Skip to main content
Top
Published in: Drugs 12/2007

01-08-2007 | Leading Article

Pharmacotherapy of Mood Disorders and Treatment Discontinuation

Author: Dr Malcolm Lader

Published in: Drugs | Issue 12/2007

Login to get access

Abstract

Depression is the most frequent and costly problem in primary care, where most of these patients are seen and treated. In many countries, the public regard antidepressant drugs as ‘addictive’, partly because of the withdrawal symptoms that can occur when they are discontinued. Indeed, discontinuation (withdrawal) symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (SSRIs). This is important because they are widely regarded as drugs of choice for both depression and the anxiety disorders. But is this true withdrawal or merely rebound? The antidepressant discontinuation syndrome is characterised by the time-locked emergence of new, clearly defined and quantifiable signs and symptoms that ensue on stopping or reducing the dose of an antidepressant. Thereby, it meets the criteria for a withdrawal syndrome. The symptoms are not usually severe or protracted. SSRIs vary in their propensity to be associated with a discontinuation syndrome: paroxetine appears to be the most likely. Patients should be warned of the possibility of developing such a reaction, but reassured that it is usually mild and self limiting. Tapering the dose, if practicable, is worthwhile. In severe cases, temporary reinstatement of the SSRI and slower tapering may be necessary. Escalation of antidepressant dosage, or ‘street abuse’, is rare with antidepressants. The use of antidepressants is generally beneficial, and efforts should be made to optimise our current use of these drugs as well as encouraging the development of newer, better and innovative compounds. To this end, physicians should educate themselves and the public about discontinuation and withdrawal, so that these clinical features can be put in a realistic context.
Literature
1.
go back to reference Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992; 14: 237–47PubMedCrossRef Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992; 14: 237–47PubMedCrossRef
2.
go back to reference Paykel ES, Hart D, Priest RG. Changes in public attitudes to depression during the Defeat Depression Campaign. Br J Psychiatry 1998; 173: 519–22PubMedCrossRef Paykel ES, Hart D, Priest RG. Changes in public attitudes to depression during the Defeat Depression Campaign. Br J Psychiatry 1998; 173: 519–22PubMedCrossRef
3.
go back to reference Kessing LV, Hansen HV, Demyttenaere K, et al. Depressive and bipolar disorders: patients’ attitudes and beliefs towards depression and antidepressants. Psychol Med 2005; 35: 1205–13PubMedCrossRef Kessing LV, Hansen HV, Demyttenaere K, et al. Depressive and bipolar disorders: patients’ attitudes and beliefs towards depression and antidepressants. Psychol Med 2005; 35: 1205–13PubMedCrossRef
4.
go back to reference Sirey JA, Bruce ML, Alexopoulos GS, et al. Stigma as a barrier to recovery: perceived stigma and patient-rated severity of illness as predictors of antidepressant drug adherence. Psychiat Serv 2001;52: 1615–20CrossRef Sirey JA, Bruce ML, Alexopoulos GS, et al. Stigma as a barrier to recovery: perceived stigma and patient-rated severity of illness as predictors of antidepressant drug adherence. Psychiat Serv 2001;52: 1615–20CrossRef
5.
go back to reference Van Voorhees BW, Fogel J, Houston TK, et al. Beliefs and attitudes associated with the intention to not accept the diagnosis of depression among young adults. Ann Fam Med 2005; 3: 38–46PubMedCrossRef Van Voorhees BW, Fogel J, Houston TK, et al. Beliefs and attitudes associated with the intention to not accept the diagnosis of depression among young adults. Ann Fam Med 2005; 3: 38–46PubMedCrossRef
6.
go back to reference Melfi CA, Chawla AJ, Croghan TW, et al. The effects of adherence to antidepressant treatment: guidelines on relapse and recurrence of depression. Arch Gen Psychiatry 1998; 55: 1128–32PubMedCrossRef Melfi CA, Chawla AJ, Croghan TW, et al. The effects of adherence to antidepressant treatment: guidelines on relapse and recurrence of depression. Arch Gen Psychiatry 1998; 55: 1128–32PubMedCrossRef
7.
go back to reference Demyttenaere K. Compliance during treatment with antidepressants. J Affect Disord 1997; 43: 27–39PubMedCrossRef Demyttenaere K. Compliance during treatment with antidepressants. J Affect Disord 1997; 43: 27–39PubMedCrossRef
8.
go back to reference Demyttenaere K, Enzlin P, Dewe W, et al. Compliance with antidepressants in a primary care setting, 1: beyond lack of efficacy and adverse events. J Clin Psychiatry 2001; 62 Suppl. 22: 30–3PubMed Demyttenaere K, Enzlin P, Dewe W, et al. Compliance with antidepressants in a primary care setting, 1: beyond lack of efficacy and adverse events. J Clin Psychiatry 2001; 62 Suppl. 22: 30–3PubMed
9.
go back to reference Demyttenaere K, Mesters P, Boulanger B, et al. Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine. J Affect Disord 2001; 65: 43–252CrossRef Demyttenaere K, Mesters P, Boulanger B, et al. Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine. J Affect Disord 2001; 65: 43–252CrossRef
10.
go back to reference Demyttenaere K, Haddad P. Compliance with antidepressant therapy and antidepressant discontinuation symptoms. Acta Psychiatr Scand 2000; 101 Suppl. 403: 50–9CrossRef Demyttenaere K, Haddad P. Compliance with antidepressant therapy and antidepressant discontinuation symptoms. Acta Psychiatr Scand 2000; 101 Suppl. 403: 50–9CrossRef
11.
go back to reference Medawar C. The antidepressant web: marketing depression and making medicines work. Int J Risk Saf Med 1997; 10: 75–126 Medawar C. The antidepressant web: marketing depression and making medicines work. Int J Risk Saf Med 1997; 10: 75–126
12.
go back to reference Medawar C, Herxheimer A, Bell A, et al. Paroxetine: panorama and user reporting of ADRs. Int J Risk Saf Med 2002; 15: 161–9 Medawar C, Herxheimer A, Bell A, et al. Paroxetine: panorama and user reporting of ADRs. Int J Risk Saf Med 2002; 15: 161–9
13.
go back to reference Taylor D, Stewart S, Connolly A. Antidepressant withdrawal symptoms: telephone calls to a national medication helpline. J Affect Disord 2006; 95: 129–33PubMedCrossRef Taylor D, Stewart S, Connolly A. Antidepressant withdrawal symptoms: telephone calls to a national medication helpline. J Affect Disord 2006; 95: 129–33PubMedCrossRef
15.
go back to reference Mitchell AJ. High medication discontinuation rates in psychiatry: how often is it understandable? J Clin Psychopharmacol 2006; 26: 109–12PubMedCrossRef Mitchell AJ. High medication discontinuation rates in psychiatry: how often is it understandable? J Clin Psychopharmacol 2006; 26: 109–12PubMedCrossRef
16.
go back to reference Blier P, Tremblay P. Physiologic mechanisms underlying the antidepressant discontinuation syndrome. J Clin Psychiatry 2006; 67 Suppl. 4: 8–13PubMed Blier P, Tremblay P. Physiologic mechanisms underlying the antidepressant discontinuation syndrome. J Clin Psychiatry 2006; 67 Suppl. 4: 8–13PubMed
17.
go back to reference Weiler I. Report of the Committee on Safety of Medicines Expert Working Group on the safety of selective serotonin reuptake inhibitor antidepressants. London: London Stationery Office, 2005 Weiler I. Report of the Committee on Safety of Medicines Expert Working Group on the safety of selective serotonin reuptake inhibitor antidepressants. London: London Stationery Office, 2005
18.
go back to reference Schatzberg A, Haddad P, Kaplan E, et al. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. J Clin Psychiatry 1997; 58 Suppl. 7: 5–10PubMed Schatzberg A, Haddad P, Kaplan E, et al. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. J Clin Psychiatry 1997; 58 Suppl. 7: 5–10PubMed
19.
go back to reference Shelton RC. The nature of the discontinuation syndrome associated with antidepressant drugs. J Clin Psychiatry 2006; 67 Suppl. 4: 3–7PubMed Shelton RC. The nature of the discontinuation syndrome associated with antidepressant drugs. J Clin Psychiatry 2006; 67 Suppl. 4: 3–7PubMed
20.
go back to reference Tyrer P. Invited comment. Acta Psychiatr Scand 2000; 102: 467–8 Tyrer P. Invited comment. Acta Psychiatr Scand 2000; 102: 467–8
21.
go back to reference Lader M. Discontinuing SSRI antidepressants: prediction, assessment and management of symptoms. Neuropsychiatr Dis Treat 2006; 2 Suppl. 1: 13–20 Lader M. Discontinuing SSRI antidepressants: prediction, assessment and management of symptoms. Neuropsychiatr Dis Treat 2006; 2 Suppl. 1: 13–20
22.
go back to reference Black K, Shea C, Dursun S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25: 255–61PubMed Black K, Shea C, Dursun S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25: 255–61PubMed
23.
go back to reference Haddad P. The SSRI discontinuation syndrome. J Psychopharmacol 1998; 2: 305–13CrossRef Haddad P. The SSRI discontinuation syndrome. J Psychopharmacol 1998; 2: 305–13CrossRef
24.
go back to reference Warner CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Family Physician 2006; 74: 449–56 Warner CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Family Physician 2006; 74: 449–56
25.
go back to reference Tamam L, Ozpoyraz N. Selective serotonin reuptake inhibitor discontinuation syndrome: a review. Adv Ther 2002; 19: 17–26PubMedCrossRef Tamam L, Ozpoyraz N. Selective serotonin reuptake inhibitor discontinuation syndrome: a review. Adv Ther 2002; 19: 17–26PubMedCrossRef
26.
go back to reference van Geffen ECG, Hugtenburg JG, Heerdink ER, et al. Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation. Eur J Clin Pharmacol 2005; 61: 303–7PubMedCrossRef van Geffen ECG, Hugtenburg JG, Heerdink ER, et al. Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation. Eur J Clin Pharmacol 2005; 61: 303–7PubMedCrossRef
27.
go back to reference Haddad P, Lejoyeux M, Young A. Antidepressant discontinuation reactions are preventable and simple to treat. Br Med J 1998; 316: 1105–6CrossRef Haddad P, Lejoyeux M, Young A. Antidepressant discontinuation reactions are preventable and simple to treat. Br Med J 1998; 316: 1105–6CrossRef
28.
go back to reference Schatzberg A, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry 2006; 67 Suppl. 4: 27–30PubMed Schatzberg A, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry 2006; 67 Suppl. 4: 27–30PubMed
29.
go back to reference Price J, Waller P, Wood S, et al. A comparison of the postmarketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br J Clin Pharmacol 1996; 42: 757–63PubMedCrossRef Price J, Waller P, Wood S, et al. A comparison of the postmarketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br J Clin Pharmacol 1996; 42: 757–63PubMedCrossRef
30.
go back to reference Haddad P, Anderson I, Rosenbaum J. Antidepressant discontinuation syndromes. In: Haddad P, Dursun S, Deakin B, editors. Adverse syndromes and psychiatric drugs. Oxford: Oxford University Press, 2004: 184–205 Haddad P, Anderson I, Rosenbaum J. Antidepressant discontinuation syndromes. In: Haddad P, Dursun S, Deakin B, editors. Adverse syndromes and psychiatric drugs. Oxford: Oxford University Press, 2004: 184–205
31.
go back to reference Rosenbaum J, Fava M, Hood S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomised clinical trial. Biol Psychiatry 1998; 44: 75–6CrossRef Rosenbaum J, Fava M, Hood S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomised clinical trial. Biol Psychiatry 1998; 44: 75–6CrossRef
32.
go back to reference Hindmarch I, Kimber S, Cockle S. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance. Int Clin Psychopharmacol 2000; 15: 305–18PubMedCrossRef Hindmarch I, Kimber S, Cockle S. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance. Int Clin Psychopharmacol 2000; 15: 305–18PubMedCrossRef
33.
go back to reference Judge R, Parry M, Quail D, et al. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol 2004; 19: 217–25 Judge R, Parry M, Quail D, et al. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol 2004; 19: 217–25
34.
go back to reference Zajecka J, Fawcett J, Amsterdam J, et al. Safety of abrupt discontinuation of fluoxetine: a randomised, placebo-controlled study. J Clin Psychopharmacol 1998; 18: 193–7PubMedCrossRef Zajecka J, Fawcett J, Amsterdam J, et al. Safety of abrupt discontinuation of fluoxetine: a randomised, placebo-controlled study. J Clin Psychopharmacol 1998; 18: 193–7PubMedCrossRef
35.
go back to reference Himei A, Okamura T. Discontinuation syndrome associated with paroxetine in depressed patients: a retrospective analysis of factors involved in the occurrence of the syndrome. CNS Drugs 2006; 20: 665–72PubMedCrossRef Himei A, Okamura T. Discontinuation syndrome associated with paroxetine in depressed patients: a retrospective analysis of factors involved in the occurrence of the syndrome. CNS Drugs 2006; 20: 665–72PubMedCrossRef
36.
go back to reference Montgomery S, Kennedy S, Burrows G, et al. Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomised double-blind placebo-controlled discontinuation study. Int Clin Psychopharmacol 2002; 17: 271–80 Montgomery S, Kennedy S, Burrows G, et al. Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomised double-blind placebo-controlled discontinuation study. Int Clin Psychopharmacol 2002; 17: 271–80
37.
go back to reference Baldwin D, Mongomery SA, Nil R, et al. Discontinuation symptoms in depression and anxiety disorders. Int J Neuropsy-chopharmacol 2005; 10: 73–84CrossRef Baldwin D, Mongomery SA, Nil R, et al. Discontinuation symptoms in depression and anxiety disorders. Int J Neuropsy-chopharmacol 2005; 10: 73–84CrossRef
38.
go back to reference Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005; 365: 482–7PubMed Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005; 365: 482–7PubMed
39.
go back to reference Moncrieff J, Wessely S, Hardy R. Meta-analysis of trials comparing antidepressants with active placebos. Br J Psychiat 1998; 172: 227–31CrossRef Moncrieff J, Wessely S, Hardy R. Meta-analysis of trials comparing antidepressants with active placebos. Br J Psychiat 1998; 172: 227–31CrossRef
40.
go back to reference Quitkin FM, Rabkin JG, Gerald J, et al. Validity of clinical trials of antidepressants. Am J Psychiat 2000; 157: 327–37PubMedCrossRef Quitkin FM, Rabkin JG, Gerald J, et al. Validity of clinical trials of antidepressants. Am J Psychiat 2000; 157: 327–37PubMedCrossRef
41.
42.
go back to reference Whittal ML, Otto MW, Hong JJ. Cognitive-behavior therapy for discontinuation of SSRI treatment of panic disorder; a case series. Behav Res Ther 2001; 39: 939–45PubMedCrossRef Whittal ML, Otto MW, Hong JJ. Cognitive-behavior therapy for discontinuation of SSRI treatment of panic disorder; a case series. Behav Res Ther 2001; 39: 939–45PubMedCrossRef
43.
go back to reference Young AH, Currie A. Physicians’ knowledge of antidepressant withdrawal effects: a survey. J Clin Psychiat 1997; 58 Suppl. 7: 28–30 Young AH, Currie A. Physicians’ knowledge of antidepressant withdrawal effects: a survey. J Clin Psychiat 1997; 58 Suppl. 7: 28–30
44.
go back to reference Khan A, Kelly R, Gill M. Survey of symptoms associated with antidepressant discontinuation. Irish J Psych Med 1999; 16: 84–9 Khan A, Kelly R, Gill M. Survey of symptoms associated with antidepressant discontinuation. Irish J Psych Med 1999; 16: 84–9
45.
go back to reference Demyttenaere K. Quality of life in depression and anxiety: does it matter? Int J Psychiat Clin Practice 2006; 10 Suppl. 1: 27–30CrossRef Demyttenaere K. Quality of life in depression and anxiety: does it matter? Int J Psychiat Clin Practice 2006; 10 Suppl. 1: 27–30CrossRef
46.
go back to reference Bosker FJ, Westerink BHC, Cremers TIF, et al. Future antidepressants: what is in the pipeline and what is missing? CNS Drugs 2004; 18: 705–32PubMedCrossRef Bosker FJ, Westerink BHC, Cremers TIF, et al. Future antidepressants: what is in the pipeline and what is missing? CNS Drugs 2004; 18: 705–32PubMedCrossRef
Metadata
Title
Pharmacotherapy of Mood Disorders and Treatment Discontinuation
Author
Dr Malcolm Lader
Publication date
01-08-2007
Publisher
Springer International Publishing
Published in
Drugs / Issue 12/2007
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200767120-00001

Other articles of this Issue 12/2007

Drugs 12/2007 Go to the issue

Adis Drug Evaluation

Aliskiren