Fluphenazine + Nortriptyline interactions

Food & lifestyle

• alcohol

  Moderate

  Metabolism

  Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

  What to do: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

  7 sources

  1. Dorian P, Sellers EM, Reed KL, et al. "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol 25 (1983): 325-31
  2. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol 24 (1983): 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther 43 (1988): 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther 17 (1975): 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol 51 (1990): 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA "Imipramine disposition in alcoholics." J Clin Psychopharmacol 2 (1982): 2-7

• alcohol

  Moderate

  Synergy

  Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines.

  What to do: Patients should be advised to avoid alcohol during phenothiazine therapy.

  2 sources

  1. Lutz EG "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA 236 (1976): 2422-3
  2. Freed E "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust 2 (1981): 44-5

Conditions

Conditions in which Fluphenazine + Nortriptyline needs care, as documented in this source.

• Acute Myocardial Infarction Recovery

  Major

  The use of most tricyclic antidepressants is contraindicated in patients that are going through the acute recovery period after a myocardial infarction.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Alcoholic Intoxication

  Major

  The use of phenothiazines is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of phenothiazines may be additive with those of alcohol. Severe respiratory depression and respiratory arrest may occur. Therapy with phenothiazines should be administered cautiously in patients who might be prone to acute alcohol intake.

  13 sources

  1. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  2. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  3. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  4. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  5. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  6. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  7. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  8. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  10. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  11. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  12. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  13. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Anticholinergic Syndrome

  Major

  Tricyclic and tetracyclic antidepressants (TCAs) have anticholinergic activity, to which elderly patients are particularly sensitive. Tertiary amines such as amitriptyline and trimipramine tend to exhibit greater anticholinergic effects than other agents in the class. Therapy with TCAs should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. In patients with angle-closure glaucoma, even average doses can precipitate an attack. Glaucoma should be treated and under control prior to initiation of therapy with TCAs, and intraocular pressure monitored during therapy.

  33 sources

  1. Remick RA, Campos PE, Misri S, Miles JE, Van Wyck, Fleet J "A comparison of the safety and efficacy of buproprion HCL and amitriptyline HCL in depressed outpatients." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 523-7
  2. Guy W, McEvoy JM, Ban TA, Wilson WH, Pate K "A double-blind clinical trial of mianserin versus amitriptyline: differentiation by adverse symptomatology." Pharmacotherapy 3 (1983): 45-51
  3. Bryant SG, Fisher S, Kluge RM "Long-term versus short-term amitriptyline side effects as measured by a postmarketing surveillance system." J Clin Psychopharmacol 7 (1987): 78-82
  4. Pedersen JH, Sorensen JL "Therapeutic effect and side effects in patients with endogenous depression treated with oral nortriptyline once a day." Neuropsychobiology 6 (1980): 42-7
  5. Georgotas A, McCue RE, Hapworth W, et al. "Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly." Biol Psychiatry 21 (1986): 1155-66
  6. Rudorfer MV, Young RC "Anticholinergic effects and plasma desipramine levels." Clin Pharmacol Ther 28 (1980): 703-6
  7. Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowes MB "Major adverse reactions during desipramine treatment." Arch Gen Psychiatry 39 (1982): 1055-61
  8. Remick RA, Keller FD, Buchanan RA, Gibson RE, Fleming JA "A comparison of the efficacy and safety of alprazolam and desipramine in depressed outpatients." Can J Psychiatry 33 (1988): 590-4

  Show all 33 sourcesShow fewer sources

  9. Ayd FJ, Jr "Long-term treatment of chronic depression: 15-year experience with doxepin HCl." J Clin Psychiatry 45 (1984): 39-46
  10. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  11. Gershon S "Comparative side effect profiles of trazodone and imipramine: special reference to the geriatric population." Psychopathology 17 (1984): 39-50
  12. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  13. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  14. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  15. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  16. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  17. Judd FK, Moore K, Norman TR, Burrows GD, Gupta RK, Parker G "A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness." Aust N Z J Psychiatry 27 (1993): 49-55
  18. Feighner JP, Cohn JB, Fabre LF, Jr Fieve RR, Mendels J, Shrivastava RK, Dunbar GC "A study comparing paroxetine placebo and imipramine in depressed patients." J Affect Disord 28 (1993): 71-9
  19. Rosen J, Pollock BG, Altieri LP, Jonas EA "Treatment of nortriptyline's side effects in elderly patients: a double-blind study of bethanechol." Am J Psychiatry 150 (1993): 1249-51
  20. Pigott TA, Pato MT, Bernstein SE, Grover GN, Hill JL, Tolliver TJ, Murphy DL "Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral and biological results." Arch Gen Psychiatry 47 (1990): 926-32
  21. Guillibert E, Pelicier Y, Archambault JC, Chabannes JP, Clerc G, Desvilles M, Guibert M, Pagot R, Poisat JL, Thobie Y "A double-blind, multicentre study of paroxetine versus clomipramine in depressed elderly patients." Acta Psychiatr Scand Suppl 350 (1989): 132-4
  22. Hermesh H, Aizenberg D, Weizman A, Lapidot M, Munitz H "Clomipramine-induced urinary dysfunction in an obsessive-compulsive adolescent." Drug Intell Clin Pharm 21 (1987): 877-9
  23. Ananth J, Assalian P, Links PS "Intolerable side effects of clomipramine." J Clin Psychopharmacol 2 (1982): 215-6
  24. Jenike MA, Baer L, Greist JH "Clomipramine versus fluoxetine in obsessive-compulsive disorder: a retrospective comparison of side effects and efficacy." J Clin Psychopharmacol 10 (1990): 122-4
  25. Claghorn JL, Feighner JP "A double-blind comparison of paroxetine with imipramine in the long-term treatment of depression." J Clin Psychopharmacol 13 (1993): S23-7
  26. Ritch R, Krupin T, Henry C, Kurata F "Oral imipramine and acute angle closure glaucoma." Arch Ophthalmol 112 (1994): 67-8
  27. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  28. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  29. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  30. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  31. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):
  32. Settle EC "Antidepressant drugs: disturbing and potentially dangerous adverse effects." J Clin Psychiatry 59 Suppl 16 (1998): 25-30
  33. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Cardiovascular Diseases

  Major

  Tricyclic and tetracyclic antidepressants (TCAs) may cause orthostatic hypotension, reflex tachycardia, syncope, and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Imipramine appears to have the greatest propensity to induce these effects, while secondary amines such as nortriptyline may do so less frequently. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, collapse and sudden death have occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include tachycardia, arrhythmias, heart block, hypertension, thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with TCAs should be avoided during the acute recovery phase following myocardial infarction, and should be administered only with extreme caution in patients with hyperthyroidism, a history of cardiovascular or cerebrovascular disease, or a predisposition to hypotension. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. Many of the newer antidepressants, including bupropion and the selective serotonin reuptake inhibitors (SSRIs), are considerably less or minimally cardiotoxic and may be appropriate alternatives.

  39 sources

  1. Robinson DS, Nies A, Corcella J, Cooper TB, Spencer C, Kefover R "Cardiovascular effects of phenelzine and amitriptyline in depressed outpatients." J Clin Psychiatry 43 (1982): 8-15
  2. Veith RC, Bloom V, Bielski R, Friedel RO "ECG effects of comparable plasma concentrations of desipramine and amitriptyline." J Clin Psychopharmacol 2 (1982): 394-8
  3. Dunn FG "Malignant hypertension associated with use of amitriptyline hydrochloride." South Med J 75 (1982): 1124-5
  4. Christensen P, Thomsen HY, Pedersen OL, et al. "Cardiovascular effects of amitriptyline in the treatment of elderly depressed patients." Psychopharmacology (Berl) 87 (1985): 212-5
  5. Pedersen JH, Sorensen JL "Therapeutic effect and side effects in patients with endogenous depression treated with oral nortriptyline once a day." Neuropsychobiology 6 (1980): 42-7
  6. Roose SP, Glassman AH, Siris SG, Walsh BT, Bruno RL, Wright LB "Comparison of imipramine- and nortriptyline-induced orthostatic hypotension: a meaningful difference." J Clin Psychopharmacol 1 (1981): 316-9
  7. Young RC, Alexopoulos GS, Shamoian CA, Dhar AK, Kutt H "Heart failure associated with high plasma 10-hydroxynortriptyline levels." Am J Psychiatry 141 (1984): 432-3
  8. Georgotas A, McCue RE, Hapworth W, et al. "Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly." Biol Psychiatry 21 (1986): 1155-66

  Show all 39 sourcesShow fewer sources

  9. Gross JS, Zwerin G "Left bundle branch block developing in a patient with sub-therapeutic nortriptyline levels: a case report." J Am Geriatr Soc 39 (1991): 1006-7
  10. Rudorfer MV, Young RC "Desipramine: cardiovascular effects and plasma levels." Am J Psychiatry 137 (1980): 984-6
  11. Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowes MB "Major adverse reactions during desipramine treatment." Arch Gen Psychiatry 39 (1982): 1055-61
  12. Carpenter P, Gobel FL, Hulsing DJ "Desipramine cardiac toxicity." Minn Med 65 (1982): 231-4
  13. Luchins DJ "Review of clinical and animal studies comparing the cardiovascular effects of doxepin and other tricyclic antidepressants." Am J Psychiatry 140 (1983): 1006-9
  14. Roose SP, Dalack GW, Glassman AH, Woodring S, Walsh BT, Giardina EG "Is doxepin a safer tricyclic for the heart?" J Clin Psychiatry 52 (1991): 338-41
  15. Burrows GD, Vohra J, Hunt D, Sloman JG, Scoggins BA, Davies B "Cardiac effects of different tricyclic antidepressant drugs." Br J Psychiatry 129 (1976): 335-41
  16. Linnoila M, Jobson KO, Gilliam JH, Paine RL "Effects of doxepin on blood pressure and heart rate in patients with primary major affective disorder ." J Clin Psychopharmacol 2 (1982): 433-4
  17. Strasberg B, Coelho A, Welch W, Swiryn S, Bauernfeind R, Rosen K "Doxepin induced torsade de pointes." Pacing Clin Electrophysiol 5 (1982): 873-7
  18. Appelbaum PS, Kapoor W "Imipramine-induced vasospasm: a case report." Am J Psychiatry 140 (1983): 913-5
  19. Kantor SJ, Glassman AH, Bigger JT, Jr Perel JM, Giardina EV "The cardiac effects of therapeutic plasma concentrations of imipramine." Am J Psychiatry 135 (1978): 534-8
  20. Ramanathan KB, Davidson C "Cardiac arrhythmia and imipramine therapy." Br Med J 1 (1975): 661-2
  21. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  22. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  23. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  24. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  25. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  26. Bluhm RE, Wilkinson GR, Shelton R, Branch RA "Genetically determined drug-metabolizing activity and desipramine- associated cardiotoxicity: a case report." Clin Pharmacol Ther 53 (1993): 89-95
  27. Laird LK, Lydiard RB, Morton WA, Steele TE, Kellner C, Thompson NM, Ballenger JC "Cardiovascular effects of imipramine, fluvoxamine, and placebo in depressed outpatients." J Clin Psychiatry 54 (1993): 224-8
  28. Feighner JP, Cohn JB, Fabre LF, Jr Fieve RR, Mendels J, Shrivastava RK, Dunbar GC "A study comparing paroxetine placebo and imipramine in depressed patients." J Affect Disord 28 (1993): 71-9
  29. Van Sweden B "Rebound antidepressant cardiac arrhythmia." Biol Psychiatry 24 (1988): 363-4
  30. Faravelli C, Brat A, Marchetti G, Franchi F, Padeletti L, Michelucci A, Pastorino A "Cardiac effects of clomipramine treatment. ECG and left ventricular systolic time intervals." Neuropsychobiology 9 (1983): 113-8
  31. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  32. Roos JC "Cardiac effects of antidepressant drugs. A comparison of the tricyclic antidepressants and fluvoxamine." Br J Clin Pharmacol 15 Suppl 3 (1983): s439-45
  33. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  34. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  35. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  36. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):
  37. Settle EC "Antidepressant drugs: disturbing and potentially dangerous adverse effects." J Clin Psychiatry 59 Suppl 16 (1998): 25-30
  38. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):
  39. Upward JW, Edwards JG, Goldie A, Waller DG "Comparative effects of fluoxetine and amitriptyline on cardiac function." Br J Clin Pharmacol 26 (1988): 399-402

• Cardiovascular Diseases

  Major

  Phenothiazines may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope, and dizziness, particularly after the first parenteral dose but rarely after the first oral dose. Low-potency agents such as chlorpromazine and thioridazine are more likely to induce these effects, which usually subside within the first couple of hours following administration. Tolerance to the hypotensive effects often develops after a few doses. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include edema, thrombosis, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with phenothiazines should be avoided or otherwise administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since phenothiazines can reverse its vasopressor effects and cause a further lowering of blood pressure.

  24 sources

  1. Varia I, Krishnan R, Davidson J "Deep-vein thrombosis with antipsychotic drugs." Psychosomatics 24 (1983): 1097-8
  2. Schreiber G, Belmaker R "In vivo differentiation of cardiac vagal blocking effects of chlorpromazine and haloperidol." Biol Psychiatry 22 (1987): 1417-21
  3. Witz L, Shapiro M, Shenkman L "Chlorpromazine induced fluid retention masquerading as idiopathic oedema." Br Med J 294 (1987): 807-8
  4. Dorson P, Crismon M "Chlorpromazine accumulation and sudden death in a patient with renal insufficiency." Drug Intell Clin Pharm 22 (1988): 776-8
  5. Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274
  6. Stevenson R, Blanshard C, Patterson D "Ventricular fibrillation due to lithium withdrawal: an interaction with chlorpromazine?" Postgrad Med J 65 (1989): 936-8
  7. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  8. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):

  Show all 24 sourcesShow fewer sources

  9. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  10. Fletcher GF, Kazamias TM "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J 78 (1969): 135-8
  11. Margolis J "Massive edema induced by thioridazine (Mellaril): an unusual complication." J Am Geriatr Soc 20 (1972): 593-4
  12. Kumar BB "Letter: Acute hypotension from thioridazine." JAMA 234 (1975): 1321
  13. Jones J, Sklar D, Dougherty J, White W "Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache." JAMA 261 (1989): 1174-6
  14. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  15. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  16. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  17. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  18. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  19. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  20. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  21. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  22. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  23. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):
  24. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Craniocerebral Trauma

  Major

  The use of phenothiazines is contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic involvement. Phenothiazines can interfere with thermoregulatory mechanisms, and a hyperthermic reaction with temperatures in excess of 104 F may occur in such patients, sometimes not until 14 to 16 hours after drug administration.

  13 sources

  1. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  2. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  3. Dilsaver SC "Effects of neuroleptics on body temperature" J Clin Psychiatry 49 (1988): 78-9
  4. Caroff S, Rosenberg H, Gerber JC "Neuroleptic malignant syndrome and malignant hyperthermia" Lancet 1 (1983): 244
  5. Keshavan MS, Kambhampati RK "Prolonged fever without extrapyramidal symptoms during neuroleptic treatment" J Clin Psychopharmacol 9 (1989): 230-1
  6. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  7. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  8. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  10. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  11. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  12. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  13. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Dementia

  Major

  Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo. These agents are not approved for the treatment of patients with dementia-related psychosis.

  14 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Nuplazid (pimavanserin)." Accelis Pharma (2016):
  14. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Depressive Disorder

  Major

  Adult and pediatric patients with depression may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Families and caregivers should be advised of the need for close observation and communication with the treating physician. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Epilepsy

  Major

  Tricyclic antidepressants (TCAs), can lower the seizure threshold and trigger seizures. These drugs should be used with extreme caution in patients with a history of seizures, or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. Daily dose restrictions might apply for specific antidepressants. Physicians are encouraged to get additional dosing recommendations on the manufacturer's prescribing information.

  9 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

  Show all 9 sourcesShow fewer sources

  9. Settle EC "Antidepressant drugs: disturbing and potentially dangerous adverse effects." J Clin Psychiatry 59 Suppl 16 (1998): 25-30

• Pheochromocytoma

  Major

  Tricyclic and tetracyclic antidepressants (TCAs) may potentiate the effects of circulating catecholamines. Enhanced sympathetic activity can provoke hypertensive crises in patients with pheochromocytoma or other tumors of the adrenal medulla, such as some neuroblastomas. Therapy with TCAs should be administered cautiously in patients with these tumors.

  12 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  5. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  6. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  7. "Product Information. Remeron (mirtazapine)." Organon (2001):
  8. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  10. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):
  11. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Respiratory Insufficiency

  Major

  The use of phenothiazines is contraindicated in comatose patients and patients with severe central nervous system depression. Phenothiazines may potentiate the CNS and respiratory depression in these patients.

  13 sources

  1. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  2. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  3. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  4. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  5. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  6. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  7. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  8. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  10. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  11. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  12. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  13. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Alcoholic Intoxication

  Moderate

  Tricyclic antidepressants can enhance the response to alcohol. In patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Anticholinergic Syndrome

  Moderate

  Phenothiazines have anticholinergic activity, to which elderly patients are particularly sensitive. Low-potency agents such as chlorpromazine and thioridazine tend to exhibit greater anticholinergic effects than other agents in the class. Therapy with phenothiazines should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders.

  11 sources

  1. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  2. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  3. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  4. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  5. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  6. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  7. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  8. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  10. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):
  11. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Bipolar Disorder

  Moderate

  A major depressive episode can be the initial presentation of bipolar disorder. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment with a tricyclic antidepressant. This screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that tricyclic antidepressants are not approved for use in treating bipolar depression.

  9 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

  Show all 9 sourcesShow fewer sources

  9. Settle EC "Antidepressant drugs: disturbing and potentially dangerous adverse effects." J Clin Psychiatry 59 Suppl 16 (1998): 25-30

• Bone Marrow Failure Disorders

  Moderate

  The use of tricyclic and tetracyclic antidepressants (TCAs) has rarely been associated with bone marrow suppression. Leukopenia, agranulocytosis, thrombocytopenia, anemia, eosinophilia, purpura, and pancytopenia have been reported with some TCAs. Patients with preexisting bone marrow suppression or blood dyscrasias receiving TCAs should be monitored closely during therapy for further decreases in blood counts.

  16 sources

  1. Draper BM, Manoharan A "Neutropenia with cross-intolerance between two tricyclic antidepressant agents." Med J Aust 146 (1987): 452-3
  2. Wolf B, Conradty M, Grohmann R, Ruther E, Witzgall H, Londong V "A case of immune complex hemolytic anemia, thrombocytopenia, and acute renal failure associated with doxepin use." J Clin Psychiatry 50 (1989): 99-100
  3. Albertini RS, Penders TM "Agranulocytosis associated with tricyclics." J Clin Psychiatry 39 (1978): 483-5
  4. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  5. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  6. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  7. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  8. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):

  Show all 16 sourcesShow fewer sources

  9. Hunt KA, Resnick MP "Clomipramine-induced agranulocytosis and its treatment with G-CSF." Am J Psychiatry 150 (1993): 522-3
  10. Magni G, Urbani A, Silvestro A, Grassetto M "Clomipramine-induced pancytopenia." J Nerv Ment Dis 175 (1987): 309-10
  11. Souhami RL, Ashton CR, Lee-Potter JP "Agranulocytosis and systemic candidiasis following clomipramine therapy." Postgrad Med J 52 (1976): 472-4
  12. Gravenor DS, Leclerc JR, Blake G "Tricyclic antidepressant agranulocytosis." Can J Psychiatry 31 (1986): 661
  13. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  14. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  15. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  16. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Breast Neoplasms

  Moderate

  The chronic use of phenothiazines is associated with persistent elevations in prolactin levels. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Therapy with phenothiazines should be administered cautiously in patients with existing or suspected malignancy of the breast.

  16 sources

  1. Ash PR, Bouma D "Exaggerated hyperprolactinemia in response to thiothixene ." Arch Neurol 38 (1981): 534-5
  2. Ristic PI, Ory SJ, Lurain JR "Endometrial adenocarcinoma associated with drug-induced hyperprolactinemia." Obstet Gynecol 67 (1986): s86-8
  3. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  4. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  5. Kane JM "Antipsychotic drug side effects: their relationship to dose." J Clin Psychiatry 46 (1985): 16-21
  6. Gift T, Plum K, Price M "Depot fluphenazine and plasma prolactin." Prog Neuropsychopharmacol Biol Psychiatry 9 (1985): 407-12
  7. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  8. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  10. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  11. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  12. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  13. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  14. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  15. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  16. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Diabetes Mellitus

  Moderate

  Both elevation and lowering of blood sugar levels have been reported with the use of some tricyclic antidepressants (TCAs). Rarely, these effects have also occurred with maprotiline, a tetracyclic antidepressant. Patients with diabetes should be monitored for worsening control of blood glucose when treated with these agents, particularly during dosage escalation or whenever dosage has been altered.

  11 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  5. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  6. Zogno MG, Tolfo L, Draghi E "Hypoglycemia caused by maprotiline in a patient taking oral antidiabetics." Ann Pharmacother 28 (1994): 406
  7. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  8. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  10. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  11. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Diabetes Mellitus

  Moderate

  There have been reports of both elevation and lowering of blood sugar levels in patients receiving tricyclic antidepressants. These drugs should be used with caution in patients with hypoglycemia, hyperglycemia or diabetes. Monitoring sugar levels is recommended.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Dystonic Disorders

  Moderate

  Phenothiazines may cause acute, dose-related dystonic reactions secondary to central dopaminergic blockade. These reactions are characterized by spastic contraction of discrete muscle groups and may include torticollis, opisthotonos, carpopedal spasm, trismus, difficulty swallowing, perioral spasms with protrusion of the tongue, and oculogyric crisis. Onset is usually within 24 to 96 hours following initiation of therapy or an increase in dosage. Risk factors include young age, male gender, use of high-potency agents (e.g., fluphenazine, perphenazine, trifluoperazine), high dosages, and IM administration. Therapy with phenothiazines should be administered cautiously in patients, particularly children, with hypocalcemia or severe dehydration, since these patients may be more susceptible to dystonic reactions. Most symptoms subside within a few hours and are almost always reversible within 24 to 48 hours following withdrawal of therapy. However, severe reactions such as laryngospasm may be life-threatening and require appropriate supportive therapy. Parenteral administration of an anticholinergic antiparkinsonian agent (e.g., benztropine, trihexyphenidyl) or diphenhydramine usually produces a prompt response and may be given orally for short-term maintenance to prevent recurrence of symptoms if phenothiazine therapy must be continued.

  31 sources

  1. Wood G, Waters A "Prolonged dystonic reaction to chlorpromazine in myxoedema coma." Postgrad Med J 56 (1980): 192-3
  2. Nahata MC, Clotz MA, Krogg EA "Adverse effects of meperidine, promethazine, and chlorpromazine for sedation in pediatric patients." Clin Pediatr (Phila) 24 (1985): 558-60
  3. Schwinghammer TL, Kroboth FJ, Juhl RP "Extrapyramidal reaction secondary to oral promethazine." Clin Pharm 3 (1984): 83-5
  4. Marcotte DB "Neuroleptics and neurologic reactions." South Med J 66 (1973): 321-4
  5. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  6. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  7. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  8. Idzorek S "Antiparkinsonian agents and fluphenazine decanoate." Am J Psychiatry 133 (1976): 80-2

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  9. Bailie GR, Nelson MV, Krenzelok EP, Lesar T "Unusual treatment response of a severe dystonia to diphenhydramine." Ann Emerg Med 16 (1987): 705-8
  10. West D "Dangers of fluphenazine." Br J Psychiatry 117 (1970): 718-9
  11. Curson DA, Barnes TR, Bamber RW, Platt SD, Hirsch SR, Duffy JC "Long-term depot maintenance of chronic schizophrenic out-patients: the seven year follow-up of the Medical Research Council fluphenazine/placebo trial. II. The incidence of compliance problems,side-effects, neurotic symptoms and depression" Br J Psychiatry 146 (1985): 469-74
  12. Singh H, Levinson DF, Simpson GM, Lo ES, Friedman E "Acute dystonia during fixed-dose neuroleptic treatment." J Clin Psychopharmacol 10 (1990): 389-96
  13. Oyewumi LK, Lapierre YD, Gray R, Batth S, Gelfand R "Abnormal involuntary movements in patients on long-acting neuroleptics." Prog Neuropsychopharmacol Biol Psychiatry 7 (1983): 719-23
  14. Reecer MV, Clinchot DM, Tipton DB "Drug-induced dystonia in a patient with C4 quadriplegia. Case report." Am J Phys Med Rehabil 72 (1993): 97-8
  15. Sheppard C, Merlis S "Drug-induced extrapyramidal symptoms: their incidence and treatment." Am J Psychiatry 123 (1967): 886-9
  16. Lamont S "Acute reactions to phenothiazine derivatives." Br J Anaesth 44 (1972): 539-40
  17. Schumock GT, Martinez E "Acute oculogyric crisis after administration of prochlorperazine." South Med J 84 (1991): 407-8
  18. Baker FM, Cook P "Compazine complications: a review." J Natl Med Assoc 73 (1981): 409-12
  19. Boston Collaborative Drug Surveillance Program "Drug-induced extrapyramidal symptoms." JAMA 224 (1973): 889-91
  20. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  21. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  22. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  23. Harries JR "Oculogyric crises due to phenothiazines." Br Med J 3 (1967): 241
  24. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  25. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  26. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  27. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  28. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  29. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  30. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):
  31. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Epilepsy

  Moderate

  Phenothiazines can lower the seizure threshold and induce seizures, particularly when dosages are high or increased rapidly and during the initiation of therapy. Of the phenothiazines used in the treatment of psychosis, chlorpromazine appears to have the greatest epileptogenic potential, while fluphenazine and thioridazine have the least. Therapy with phenothiazines should be administered cautiously in patients with a history of seizures or other factors predisposing to seizures such as abnormal EEG, preexisting CNS pathology, or head trauma. Adequate anticonvulsant therapy should be maintained during administration of phenothiazines.

  18 sources

  1. Markowitz J, Brown R "Seizures with neuroleptics and antidepressants." Gen Hosp Psychiatry 9 (1987): 135-41
  2. Waterhouse RG "Epileptiform convulsions in children following premedication with Pamergan SP100." Br J Anaesth 39 (1967): 268-70
  3. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  4. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  6. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  7. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  8. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):

  Show all 18 sourcesShow fewer sources

  9. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  10. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  11. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  12. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  13. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  14. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  15. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  16. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  17. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):
  18. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Glaucoma

  Moderate

  Tricyclic antidepressants as other type of antidepressants have an effect on pupil size causing dilation. This effect can potentially narrow the eye angle resulting in increased intraocular pressure and angle closure glaucoma, especially in predisposed patients. These drugs should be used with caution in patients with anatomically narrow angle or history of glaucoma. Doxepin hydrochloride capsules are contraindicated in patients with glaucoma.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Hematologic Diseases

  Moderate

  Phenothiazines may infrequently cause hematologic toxicity, including agranulocytosis, thrombocytopenia, eosinophilia, aplastic anemia, purpura, granulocytopenia, and hemolytic anemia. Mild leukopenia may occur frequently with large doses over prolonged periods but is generally reversible despite continued treatment. Therapy with phenothiazines should be administered cautiously, if at all, in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly, and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice. Most cases of agranulocytosis have occurred between the fourth and tenth weeks of therapy.

  21 sources

  1. Stein P, Inwood M "Hemolytic anemia associated with chlorpromazine therapy." Can J Psychiatry 25 (1980): 659-61
  2. Holt R "Neuroleptic drug-induced changes in platelet levels." J Clin Psychopharmacol 4 (1984): 130-2
  3. Yassa R "Agranulocytosis in the course of phenothiazine therapy." J Clin Psychiatry 46 (1985): 341-3
  4. Zengotita H, Holt R "Neuroleptic drug-induced coagulopathy: mechanism of reaction and duration of effect." J Clin Psychiatry 47 (1986): 35-7
  5. Aram H "Henoch-Schonlein purpura induced by chlorpromazine." J Am Acad Dermatol 17 (1987): 139-40
  6. Young A, Kehoe R "Two cases of agranulocytosis on addition of a butyrophenone to a long-standing course of phenothiazine treatment." Br J Psychiatry 154 (1989): 710-12
  7. Ben-Yehuda A, Bloom A, Lijhovetzky G, et al. "Chlorpromazine-induced liver and bone marrow granulomas associated with agranulocytosis." Isr J Med Sci 26 (1990): 449-51
  8. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):

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  9. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  10. Rosenthal DS, Stein GF, Santos JC "Thioridazine agranulocytosis." JAMA 200 (1967): 81-2
  11. Holt RJ "Fluphenazine decanoate-induced cholestatic jaundice and thrombocytopenia." Pharmacotherapy 4 (1984): 227-9
  12. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  13. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  14. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  15. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  16. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  17. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  18. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  19. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  20. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  21. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Kidney Diseases

  Moderate

  Phenothiazines and their metabolites are excreted by the kidney. There are very limited data concerning the use of phenothiazines in patients with renal disease. Therapy with phenothiazines should be administered cautiously in patients with significantly impaired renal function. The manufacturers recommend periodic renal function tests for all patients during prolonged therapy.

  16 sources

  1. Dorson P, Crismon M "Chlorpromazine accumulation and sudden death in a patient with renal insufficiency." Drug Intell Clin Pharm 22 (1988): 776-8
  2. Taylor G, Houston JB, Shaffer J, Mawer G "Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man." Br J Clin Pharmacol 15 (1983): 287-93
  3. Fabre J, Freudenreich J, de Duckert A, Pitton JS, Rudhardt M, Virieux C "Influence of renal insufficiency on the excretion of chloroquine, phenobarbital, phenothiazines and methacycline." Helv Med Acta 33 (1967): 307-16
  4. McAllister CJ, Scowden EB, Stone WJ "Toxic psychosis induced by phenothiazine administration in patients with chronic renal failure." Clin Nephrol 10 (1978): 191-5
  5. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  6. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  7. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  8. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  10. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  11. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  12. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  13. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  14. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  15. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  16. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Liver Diseases

  Moderate

  Tricyclic and tetracyclic antidepressants (TCAs) are known to undergo metabolism in the liver. Some of the metabolites, such as those of imipramine, clomipramine and desipramine, may be pharmacologically active. Many of the metabolites are also excreted by the kidney. There are very limited data concerning the use of TCAs in patients with renal and/or liver disease. Therapy with TCAs should be administered cautiously in patients with significantly impaired renal or hepatic function. Dosage adjustments may be necessary.

  27 sources

  1. Gram LF, Overo KF "First-pass metabolism of nortriptyline in man." Clin Pharmacol Ther 18 (1975): 305-14
  2. Nelson JC, Jatlow PI "Nonlinear desipramine kinetics: prevalence and importance." Clin Pharmacol Ther 41 (1987): 666-70
  3. Schulz P, Turner-Tamiyasu K, Smith G, Giacomini KM, Blaschke TF "Amitriptyline disposition in young and elderly normal men." Clin Pharmacol Ther 33 (1983): 360-6
  4. Midha KK, Hubbard JW, McKay G, et al. "Stereoselective pharmacokinetics of doxepin isomers." Eur J Clin Pharmacol 42 (1992): 539-44
  5. Sandoz M, Vandel S, Vandel B, et al. "Metabolism of amitriptyline in patients with chronic renal failure." Eur J Clin Pharmacol 26 (1984): 227-32
  6. Jorgensen A, Hansen V "Pharmacokinetics of amitriptyline infused intravenously in man." Eur J Clin Pharmacol 10 (1976): 337-41
  7. Henry JF, Altamura C, Gomeni R, Hervy MP, Forette F, Morselli PL "Pharmacokinetics of amitriptyline in the elderly." Int J Clin Pharmacol Ther Toxicol 19 (1981): 1-5
  8. Ciraulo DA, Barnhill JG, Jaffe JH "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther 43 (1988): 509-18

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  9. Brosen K, Gram LF "First-pass metabolism of imipramine and desipramine: impact of the sparteine oxidation phenotype." Clin Pharmacol Ther 43 (1988): 400-6
  10. Lieberman JA, Cooper TB, Suckow RF, et al. "Tricyclic antidepressant and metabolite levels in chronic renal failure." Clin Pharmacol Ther 37 (1985): 301-7
  11. Faulkner RD, Pitts WM, Lee CS, Lewis WA, Fann WE "Multiple-dose doxepin kinetics in depressed patients." Clin Pharmacol Ther 34 (1983): 509-15
  12. Ziegler VE, Biggs JT, Wylie LT, Rosen SH, Hawf DJ, Coryell WH "Doxepin kinetics." Clin Pharmacol Ther 23 (1978): 573-9
  13. Virtanen R, Scheinin M, Iisalo E "Single dose pharmacokinetics of doxepin in healthy volunteers." Acta Pharmacol Toxicol (Copenh) 47 (1980): 371-6
  14. Dawlilng S, Lynn K, Rosser R, Braithwaite R "The pharmacokinetics of nortriptyline in patients with chronic renal failure." Br J Clin Pharmacol 12 (1981): 39-45
  15. Dawling S, Crome P, Braithwaite R "Pharmacokinetics of single oral doses of nortriptyline in depressed elderly hospital patients and young healthy volunteers." Clin Pharmacokinet 5 (1980): 394-401
  16. Alexanderson B "Pharmacokinetics of nortriptyline in man after single and multiple oral doses: the predictability of steady-state plasma concentrations from single-dose plasma-level data." Eur J Clin Pharmacol 4 (1972): 82-91
  17. Gram LF, Andreasen PB, Overo KF, Christiansen J "Comparison of single dose kinetics of imipramine, nortriptyline and antipyrine in man." Psychopharmacology (Berl) 50 (1976): 21-7
  18. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  19. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  20. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  21. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  22. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  23. Linnoila M, Insel T, Kilts C, Potter WZ, Murphy DL "Plasma steady-state concentrations of hydroxylated metabolites of clomipramine." Clin Pharmacol Ther 32 (1982): 208-11
  24. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  25. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  26. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  27. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Liver Diseases

  Moderate

  In general, tricyclic antidepressants should be used with caution in patients with liver or renal disease, as these drugs are metabolized and excreted through the liver and kidneys. Dose selection, especially in the elderly patients that might have liver or renal dysfunction, should usually be limited to the smallest effective total daily dose. Some tricyclic antidepressants such as clomipramine and nortriptyline have occasionally been associated with elevations in SGOT (AST) and SGPT (ALT), and other hepatic adverse events such as jaundice. Although serious liver injury has only been reported rarely, therapy with these drugs should be administered cautiously in patients with preexisting liver disease and periodic monitoring of liver enzyme levels is recommended.

  9 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. Larrey D, Rueff B, Pessayre D, Danan G, Algard M, Geneve J, Benhamou JP "Cross hepatotoxicity between tricyclic antidepressants." Gut 27 (1986): 726-7
  6. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  7. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  8. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):

  Show all 9 sourcesShow fewer sources

  9. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Liver Diseases

  Moderate

  Phenothiazines are extensively metabolized by the liver and may accumulate in patients with hepatic impairment. In addition, the use of some phenothiazines has been associated with adverse hepatic effects including cholestatic jaundice and elevated liver enzymes, generally within the first few months of therapy. Cholestatic jaundice usually occurs between the second and fourth weeks of therapy in approximately 0.1% to 4% of all patients. Therapy with phenothiazines should be administered cautiously in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. Liver function and urine bilirubin tests should be performed periodically during prolonged therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of cholestatic jaundice such as upper abdominal pain, nausea, yellow skin, influenza-like symptoms, rash, and fever. Phenothiazine therapy should be discontinued, preferably permanently, if jaundice occurs and is attributable to the drug. Clinical recovery is usually observed within a few weeks following withdrawal of therapy, although histopathologic changes may persist for longer periods.

  28 sources

  1. Seeff L "Drug-induced chronic liver disease, with emphasis on chronic active hepatitis." Semin Liver Dis 1 (1981): 104-15
  2. Dossing M, Andreasen B "Drug-induced liver disease in Denmark." Scand J Gastroenterol 17 (1982): 205-11
  3. Bach N, Thung S, Schaffner F, Tobias H "Exaggerated cholestasis and hepatic fibrosis following simultaneous administration of chlorpromazine and sodium valproate." Dig Dis Sci 34 (1989): 1303-7
  4. Maxwell JD, Carrella M, Parkes JD, et al. "Plasma disappearance and cerebral effects of chlorpromazine in cirrhosis." Clin Sci 43 (1972): 143-51
  5. Whitfield LR, Kaul PN, Clark ML "Chlorpromazine metabolism IX: pharmacokinetics of chlorpromazine following oral administration in man." J Pharmacokinet Biopharm 6 (1978): 187-96
  6. Simpson GM, Yadalam KG, Levinson DF, et al. "Single-dose pharmacokinetics of fluphenazine after fluphenazine decanoate administration." J Clin psychopharmacol 10 (1990): 417-21
  7. Hu OY, Tang H-S, Sheeng T-Y, et al. "Pharmacokinetics of promazine I: disposition in patients with acute viral hepatitis B." Biopharm Drug Dispos 11 (1990): 557-68
  8. Taylor G, Houston JB, Shaffer J, Mawer G "Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man." Br J Clin Pharmacol 15 (1983): 287-93

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  9. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  10. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  11. Derby LE, Gutthann SP, Jick H, Dean AD "Liver disorders in patients receiving chlorpromazine or isoniazid." Pharmacotherapy 13 (1993): 353-8
  12. Chetty M, Moodley SV, Miller R "Important metabolites to measure in pharmacodynamic studies of chlorpromazine." Ther Drug Monit 16 (1994): 30-6
  13. Barancik M, Brandborg LL, Albion MJ "Thioridazine-induced cholestasis." JAMA 200 (1967): 69-70
  14. Reinhart MJ, Benson RM, Kwass SK, Storey WF "Suggestive evidence of hepatotoxicity concomitant with thioridazine hydrochloride use." JAMA 197 (1966): 767-9
  15. Snyder S "Fluphenazine jaundice. Report of a case." Am J Gastroenterol 73 (1980): 336-40
  16. Holt RJ "Fluphenazine decanoate-induced cholestatic jaundice and thrombocytopenia." Pharmacotherapy 4 (1984): 227-9
  17. Lok AS, Ng IO "Prochlorperazine-induced chronic cholestasis." J Hepatol 6 (1988): 369-73
  18. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  19. Moradpour D, Altorfer J, Flury R, Greminger P, Meyenberger C, Jost R, Schmid M "Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis." Hepatology 20 (1994): 1437-41
  20. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  21. Podevin P, Biour M "Drug-induced ''allergic hepatitis''." Clin Rev Allergy Immunol 13 (1995): 223-44
  22. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  23. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  24. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  25. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  26. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  27. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  28. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Lung Diseases

  Moderate

  Phenothiazines may suppress the cough reflex. Therapy with phenothiazines should be administered cautiously in patients with chronic respiratory disorders, including severe asthma, emphysema, or acute respiratory tract infections.

  24 sources

  1. Seeff L "Drug-induced chronic liver disease, with emphasis on chronic active hepatitis." Semin Liver Dis 1 (1981): 104-15
  2. Dossing M, Andreasen B "Drug-induced liver disease in Denmark." Scand J Gastroenterol 17 (1982): 205-11
  3. Dorson P, Crismon M "Chlorpromazine accumulation and sudden death in a patient with renal insufficiency." Drug Intell Clin Pharm 22 (1988): 776-8
  4. Bach N, Thung S, Schaffner F, Tobias H "Exaggerated cholestasis and hepatic fibrosis following simultaneous administration of chlorpromazine and sodium valproate." Dig Dis Sci 34 (1989): 1303-7
  5. Ben-Yehuda A, Bloom A, Lijhovetzky G, et al. "Chlorpromazine-induced liver and bone marrow granulomas associated with agranulocytosis." Isr J Med Sci 26 (1990): 449-51
  6. Dahl SG, Strandjord RE "Pharmacokinetics of chlorpromazine after single and chronic dosage." Clin Pharmacol Ther 21 (1977): 437-48
  7. Whitfield LR, Kaul PN, Clark ML "Chlorpromazine metabolism IX: pharmacokinetics of chlorpromazine following oral administration in man." J Pharmacokinet Biopharm 6 (1978): 187-96
  8. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):

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  9. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  11. Derby LE, Gutthann SP, Jick H, Dean AD "Liver disorders in patients receiving chlorpromazine or isoniazid." Pharmacotherapy 13 (1993): 353-8
  12. Chetty M, Moodley SV, Miller R "Important metabolites to measure in pharmacodynamic studies of chlorpromazine." Ther Drug Monit 16 (1994): 30-6
  13. Lok AS, Ng IO "Prochlorperazine-induced chronic cholestasis." J Hepatol 6 (1988): 369-73
  14. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  15. Moradpour D, Altorfer J, Flury R, Greminger P, Meyenberger C, Jost R, Schmid M "Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis." Hepatology 20 (1994): 1437-41
  16. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  17. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  18. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  19. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  20. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  21. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  22. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  23. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  24. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Neuroleptic Malignant Syndrome

  Moderate

  The central dopaminergic blocking effects of phenothiazines may precipitate or aggravate a potentially fatal symptom complex known as Neuroleptic Malignant Syndrome (NMS). NMS is observed most frequently when high-potency neuroleptic agents like haloperidol or fluphenazine are administered intramuscularly but may occur with any agent possessing neuroleptic activity given for any length of time. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Phenothiazine therapy should not be initiated in patients with active NMS and should be immediately discontinued if currently being administered in such patients. In patients with a history of NMS, introduction or reintroduction of phenothiazines should be carefully considered, since NMS may recur.

  24 sources

  1. Morris H, McCormick W, Reinarz J "Neuroleptic malignant syndrome." Arch Neurol 37 (1980): 462-3
  2. Price W, Giannini A "A paradoxical response to chlorpromazine: a possible variant of the neuroleptic malignant syndrome." J Clin Pharmacol 23 (1983): 567-9
  3. Tenenbein M "The neuroleptic malignant syndrome: occurrence in a 15-year-old boy and recovery with bromocriptine therapy." Pediatr Neurosci 12 (1985): 161-4
  4. Caroff SN "The neuroleptic malignant syndrome." J Clin Psychiatry 41 (1980): 79-83
  5. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  6. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  7. Zubenko G, Pope HG, Jr "Management of a case of neuroleptic malignant syndrome with bromocriptine." Am J Psychiatry 140 (1983): 1619-20
  8. Granato JE, Stern BJ, Ringel A, Karim AH, Krumholz A, Coyle J, Adler S "Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine." Ann Neurol 14 (1983): 89-90

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  9. Grunhaus L, Sancovici S, Rimon R "Neuroleptic malignant syndrome due to depot fluphenazine." J Clin Psychiatry 40 (1979): 99-100
  10. Dhib-Jalbut S, Hesselbrock R, Brott T, Silbergeld D "Treatment of the neuroleptic malignant syndrome with bromocriptine" JAMA 250 (1983): 484-5
  11. Caroff S, Rosenberg H, Gerber JC "Neuroleptic malignant syndrome and malignant hyperthermia" Lancet 1 (1983): 244
  12. Rampertaap MP "Neuroleptic malignant syndrome." South Med J 79 (1986): 331-6
  13. West D "Dangers of fluphenazine." Br J Psychiatry 117 (1970): 718-9
  14. Manser TJ, Warner JF "Neuroleptic malignant syndrome associated with prochlorperazine." South Med J 83 (1990): 73-4
  15. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  16. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  17. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  18. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  19. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  20. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  21. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  22. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  23. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  24. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Neutropenia

  Moderate

  The use of some tricyclic antidepressants has been associated with neutropenia (ANC < 500/mm3) and agranulocytosis (ANC < 500/mm3). Leukocyte and differential blood counts should be performed in patients that develop fever and sore throat during treatment. Therapy should be discontinued if there is evidence of pathologic neutrophil depression.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Parkinsonian Disorders

  Moderate

  The use of phenothiazines is associated with pseudo-parkinsonian symptoms such as akinesia, bradykinesia, tremors, pill-rolling motion, cogwheel rigidity, and postural abnormalities including stooped posture and shuffling gait. The onset is usually 1 to 2 weeks following initiation of therapy or an increase in dosage. Propylamino derivatives such as chlorpromazine, promazine, and triflupromazine may be more likely to induce these effects. Therapy with phenothiazines should be administered cautiously in patients with Parkinson's disease or parkinsonian symptoms.

  24 sources

  1. Rajput A, Rozdilsky B, Hornykiewicz O, et al. "Reversible drug-induced parkinsonism." Arch Neurol 39 (1982): 6446
  2. Mariani P "Adverse reactions to chlorpromazine in the treatment of migraine." Ann Emerg Med 17 (1988): 380-1
  3. Schwinghammer TL, Kroboth FJ, Juhl RP "Extrapyramidal reaction secondary to oral promethazine." Clin Pharm 3 (1984): 83-5
  4. Marcotte DB "Neuroleptics and neurologic reactions." South Med J 66 (1973): 321-4
  5. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  6. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  7. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  8. Lamb P, Mindham RH, Ezzat MA "Letter: Parkinsonism induced by fluphenazine decanoate." Lancet 1 (1976): 484

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  9. Curson DA, Barnes TR, Bamber RW, Platt SD, Hirsch SR, Duffy JC "Long-term depot maintenance of chronic schizophrenic out-patients: the seven year follow-up of the Medical Research Council fluphenazine/placebo trial. II. The incidence of compliance problems,side-effects, neurotic symptoms and depression" Br J Psychiatry 146 (1985): 469-74
  10. Oyewumi LK, Lapierre YD, Gray R, Batth S, Gelfand R "Abnormal involuntary movements in patients on long-acting neuroleptics." Prog Neuropsychopharmacol Biol Psychiatry 7 (1983): 719-23
  11. Sheppard C, Merlis S "Drug-induced extrapyramidal symptoms: their incidence and treatment." Am J Psychiatry 123 (1967): 886-9
  12. Edelstein H, Knight RT "Severe parkinsonism in two AIDS patients taking prochlorperazine." Lancet 2 (1987): 341-2
  13. Baker FM, Cook P "Compazine complications: a review." J Natl Med Assoc 73 (1981): 409-12
  14. Boston Collaborative Drug Surveillance Program "Drug-induced extrapyramidal symptoms." JAMA 224 (1973): 889-91
  15. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  16. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  17. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  18. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  19. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  20. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  21. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  22. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  23. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  24. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):

• Schizophrenia

  Moderate

  Tricyclic antidepressants (TCAs) may aggravate symptoms of psychosis in schizophrenic patients, particularly those with paranoid symptomatology. Depressed patients, usually those with bipolar disorder, may experience a switch from depression to mania or hypomania. These occurrences have also been reported rarely with the tetracyclic antidepressant, maprotiline. Therapy with these agents should be administered cautiously in patients with schizophrenia, bipolar disorder, or a history of mania.

  24 sources

  1. Hemmingsen R, Rafaelsen OJ "Hypnagogic and hypnopompic hallucinations during amitriptyline treatment." Acta Psychiatr Scand 62 (1980): 364-8
  2. Preskorn SH, Simpson S "Tricyclic-antidepressant-induced delirium and plasma drug concentration." Am J Psychiatry 139 (1982): 822-3
  3. Holmes VF, Fricchione GL "Hypomania in an AIDS patient receiving amitriptyline for neuropathic pain." Neurology 39 (1989): 305
  4. Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowes MB "Major adverse reactions during desipramine treatment." Arch Gen Psychiatry 39 (1982): 1055-61
  5. Norman TR, Judd F, Holwill BJ, Burrows GD "Doxepin and visual hallucinations." Aust N Z J Psychiatry 16 (1982): 295-6
  6. Hardoby W "Imipramine and suicidal thoughts ." Am J Psychiatry 149 (1992): 412-3
  7. Godwin CD "Case report of tricyclic-induced delirium at a therapeutic drug concentration." Am J Psychiatry 140 (1983): 1517-8
  8. Rampling D "Aggression: a paradoxical response to tricyclic antidepressants." Am J Psychiatry 135 (1978): 117-8

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  9. Kupfer DJ, Carpenter LL, Frank E "Possible role of antidepressants in precipitating mania and hypomania in recurrent depression." Am J Psychiatry 145 (1988): 804-8
  10. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  11. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  12. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  13. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  14. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  15. van Kammen DP, van Scheyen JD, Murphy DL "Platelet monoamine oxidase activity and clomipramine-induced mania in unipolar depressed patients." Biol Psychiatry 15 (1980): 565-73
  16. Vallada HP, Gentil V "Musical hallucinations triggered by clomipramine?" Br J Psychiatry 159 (1991): 888-9
  17. Harper G "Suicidality with clomipramine." J Am Acad Child Adolesc Psychiatry 31 (1992): 369-70
  18. Cruz R "Clomipramine side effects." J Am Acad Child Adolesc Psychiatry 31 (1992): 1168-9
  19. Peet M "Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants." Br J Psychiatry 164 (1994): 549-50
  20. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  21. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  22. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  23. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Schizophrenia

  Moderate

  Some tricyclic antidepressants have shown to cause activation or exacerbation of psychosis in schizophrenic patients. A dosage reduction might be required.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Tardive Dyskinesia

  Moderate

  Tricyclic and tetracyclic antidepressants (TCAs) have anticholinergic activity, to which elderly patients are particularly sensitive. Tertiary amines such as amitriptyline and trimipramine tend to exhibit greater anticholinergic effects than other agents in the class. As with other drugs that possess anticholinergic activity, TCAs may aggravate tardive dyskinesia or induce previously suppressed symptoms. Patients with tardive dyskinesia requiring therapy with TCAs should be monitored for exacerbation of the condition.

  18 sources

  1. Woogen S, Graham J, Angrist B "A tardive dyskinesia-like syndrome after amitriptyline treatment." J Clin Psychopharmacol 1 (1981): 34-6
  2. Finder E, Lin K-M, Ananth J "Dystonic reaction to amitriptyline." Am J Psychiatry 139 (1982): 1220
  3. Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowes MB "Major adverse reactions during desipramine treatment." Arch Gen Psychiatry 39 (1982): 1055-61
  4. Lee HK "Dystonic reactions to amitriptyline and doxepin ." Am J Psychiatry 145 (1988): 649
  5. Gersten SP "Tardive dyskinesia-like syndromes with clomipramine ." Am J Psychiatry 150 (1993): 165-6
  6. Schatzberg AF, Cole JO, Blumer DP "Speech blockage: a tricyclic side effect." Am J Psychiatry 135 (1978): 600-1
  7. Dekret JJ, Maany I, Ramsey TA, Mendels J "A case of oral dyskinesia associated with imipramine treatment." Am J Psychiatry 134 (1977): 1297-8
  8. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):

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  9. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  10. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  11. "Product Information. Sinequan (doxepin)." Roerig Division (2002):
  12. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  13. Sandyk R "Persistent akathisia associated with early dyskinesia." Postgrad Med J 60 (1984): 916
  14. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  15. "Product Information. Ludiomil (maprotiline)." Ciba-Geigy Pharmaceuticals (2001):
  16. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  17. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):
  18. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Tardive Dyskinesia

  Moderate

  Phenothiazines may commonly precipitate symptoms of tardive dyskinesia (TD), a syndrome consisting of rhythmic involuntary movements variously involving the tongue, face, mouth, lips, jaw, and/or trunk and extremities, following chronic use of at least several months but often years. Elderly patients, particularly women, are most susceptible. Also, propylpiperazine derivatives like fluphenazine, perphenazine, prochlorperazine, and trifluoperazine may be more likely to induce this syndrome. Both the risk of developing TD and the likelihood that it will become irreversible increase with the duration and total cumulative dose of phenothiazine therapy administered. However, patients may infrequently develop symptoms after relatively brief treatment periods at low dosages. If TD occurs during phenothiazine therapy, prompt withdrawal of the offending agent or at least a lowering of the dosage should be considered. TD symptoms usually become more severe after drug discontinuation or a dosage reduction, but may gradually improve over months to years. In patients with preexisting drug-induced TD, initiating or increasing the dosage of phenothiazine therapy may temporarily mask the symptoms of TD but may eventually worsen the condition. The newer, atypical neuroleptic agents (e.g., risperidone, quetiapine, olanzapine) tend to be associated with a substantially reduced risk of inducing TD and are considered the drugs of choice in patients being treated for psychosis.

  30 sources

  1. Yassa R, Dimitry R "Single phenothiazines and tardive dyskinesia." J Clin Psychiatry 44 (1983): 233-4
  2. Mariani P "Adverse reactions to chlorpromazine in the treatment of migraine." Ann Emerg Med 17 (1988): 380-1
  3. Yesavage JA, Tanke ED, Sheikh JI "Tardive dyskinesia and steady-state serum levels of thiothixene." Arch Gen Psychiatry 44 (1987): 913-5
  4. Schwinghammer TL, Kroboth FJ, Juhl RP "Extrapyramidal reaction secondary to oral promethazine." Clin Pharm 3 (1984): 83-5
  5. Marcotte DB "Neuroleptics and neurologic reactions." South Med J 66 (1973): 321-4
  6. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  7. "Product Information. Sparine (promazine)." Wyeth-Ayerst Laboratories (2001):
  8. Csernansky JG, Grabowski K, Cervantes J, Kaplan J, Yesavage JA "Fluphenazine decanoate and tardive dyskinesia: a possible association." Am J Psychiatry 138 (1981): 1362-5

  Show all 30 sourcesShow fewer sources

  9. Perenyi A, Arato M "Fluphenazine and tardive dyskinesia" Arch Gen Psychiatry 41 (1984): 727
  10. Mukherjee S, Rosen AM, Cardenas C, Varia V, Olarte S "Tardive dyskinesia in psychiatric outpatients: a study of prevalence and association with demographic, clinical, and drug history variables." Arch Gen Psychiatry 39 (1982): 466-9
  11. Kolakowska T, Williams AO, Ardern M "Tardive dyskinesia and current dose of neuroleptic drugs" Arch Gen Psychiatry 42 (1985): 925
  12. Glazer WM, Moore DC "The diagnosis of rapid abnormal involuntary movements associated with fluphenazine decanoate." J Nerv Ment Dis 168 (1980): 439-41
  13. McClelland HA, Metcalfe AV, Kerr TA, Dutta D, Watson P "Facial dyskinesia: a 16-year follow-up study" Br J Psychiatry 158 (1991): 691-6
  14. Curson DA, Barnes TR, Bamber RW, Platt SD, Hirsch SR, Duffy JC "Long-term depot maintenance of chronic schizophrenic out-patients: the seven year follow-up of the Medical Research Council fluphenazine/placebo trial. II. The incidence of compliance problems,side-effects, neurotic symptoms and depression" Br J Psychiatry 146 (1985): 469-74
  15. Yassa R, Iskandar H, Ally J "The prevalence of tardive dyskinesia in fluphenazine-treated patients." J Clin Psychopharmacol 8 (1988): 17S-20S
  16. Oyewumi LK, Lapierre YD, Gray R, Batth S, Gelfand R "Abnormal involuntary movements in patients on long-acting neuroleptics." Prog Neuropsychopharmacol Biol Psychiatry 7 (1983): 719-23
  17. Sheppard C, Merlis S "Drug-induced extrapyramidal symptoms: their incidence and treatment." Am J Psychiatry 123 (1967): 886-9
  18. Baker FM, Cook P "Compazine complications: a review." J Natl Med Assoc 73 (1981): 409-12
  19. Boston Collaborative Drug Surveillance Program "Drug-induced extrapyramidal symptoms." JAMA 224 (1973): 889-91
  20. "Product Information. Prolixin (fluphenazine)." Bristol-Myers Squibb (2001):
  21. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  22. "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation (2001):
  23. "Product Information. Serentil (mesoridazine)." Boehringer-Ingelheim (2001):
  24. "Product Information. Torecan (thiethylperazine)." Roxane Laboratories Inc (2001):
  25. "Product Information. Trilafon (perphenazine)." Schering Corporation (2001):
  26. "Product Information. Tacaryl (methdilazine)." Westwood Squibb Pharmaceutical Corporation (2001):
  27. "Product Information. Temaril (trimeprazine)." Allergan Inc (2001):
  28. "Product Information. Stelazine (trifluoperazine)." SmithKline Beecham (2001):
  29. "Product Information. Vesprin (triflupromazine)." Bristol-Myers Squibb (2001):
  30. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Thyroid Diseases

  Moderate

  Most tricyclic antidepressants should be administered with caution in hyperthyroid patients or those receiving thyroid medication as they may develop arrhythmias when these drugs are given.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

• Urinary Retention

  Moderate

  Due to their anticholinergic properties, tricyclic antidepressants should be administered with caution in patients with history of urinary retention. Particularly doxepin hydrochloride capsules are contraindicated in patients with tendency to urinary retention.

  8 sources

  1. "Product Information. Pamelor (nortriptyline)." Sandoz Pharmaceuticals Corporation (2002):
  2. "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals (2002):
  3. "Product Information. Norpramin (desipramine)." Hoechst Marion Roussel (2002):
  4. "Product Information. Tofranil (imipramine)." Novartis Pharmaceuticals (2002):
  5. "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals (2001):
  6. "Product Information. Asendin (amoxapine)." Lederle Laboratories (2001):
  7. "Product Information. Surmontil (trimipramine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Vivactil (protriptyline)." Merck & Co., Inc (2001):

Therapeutic duplication

Drug classes that overlap with Fluphenazine + Nortriptyline, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• antidepressants

  The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antidepressants' category.

  Example product in the source data (US market): Bupropion/dextromethorphan

• antidepressants

  The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antidepressants' category.

  Example product in the source data (US market): Fluoxetine/olanzapine

• antidepressants

  The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antidepressants' category.

  Example product in the source data (US market): Limbitrol ds

• antidepressants

  The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antidepressants' category.

  Example product in the source data (US market): Amitriptyline/perphenazine

• antidepressants

  The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antidepressants' category.

  Example product in the source data (US market): Bupropion/naltrexone

• antipsychotics

  The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antipsychotics' category.

  Example product in the source data (US market): Fluoxetine/olanzapine

• antipsychotics

  The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antipsychotics' category.

  Example product in the source data (US market): Olanzapine/samidorphan

• antipsychotics

  The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antipsychotics' category.

  Example product in the source data (US market): Amitriptyline/perphenazine