Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications

Abstract

Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to illustrate withdrawal after decrease, discontinuation, or switch of psychotropic medications based on the drug class (i.e., benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, antidepressants, ketamine, antipsychotics, lithium, mood stabilizers) according to the diagnostic criteria of Chouinard and Chouinard [Psychother Psychosom. 2015; 84 (2): 63-71], which encompass new withdrawal symptoms, rebound symptoms, and persistent post-withdrawal disorders. All these drugs may induce withdrawal syndromes and rebound upon discontinuation, even with slow tapering. However, only selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, and antipsychotics were consistently also associated with persistent post-withdrawal disorders and potential high severity of symptoms, including alterations of clinical course, whereas the distress associated with benzodiazepines discontinuation appears to be shortlived. As a result, the common belief that benzodiazepines should be substituted by medications that cause less dependence such as antidepressants and antipsychotics runs counter the available literature. Ketamine, and probably its derivatives, may be classified as at high risk for dependence and addiction. Because of the lag phase that has taken place between the introduction of a drug into the market and the description of withdrawal symptoms, caution is needed with the use of newer antidepressants and antipsychotics. Within medication classes, alprazolam, lorazepam, triazolam, paroxetine, venlafaxine, fluphenazine, perphenazine, clozapine, and quetiapine are more likely to induce withdrawal. The likelihood of withdrawal manifestations that may be severe and persistent should thus be taken into account in clinical practice and also in children and adolescents.

The Deceptive Manifestations of Treatment Resistance in Depression: A New Look at the Problem

“…Finally, before entering a trial, patients may discontinue their current antidepressant treatment. Even with slow tapering, the likelihood of withdrawal syndromes and persistent postwithdrawal disorders and symptoms is very high and the likelihood of response of these syndromes to the introduction of new antidepressants is very variable [29][30][31][32][33].…”

The ‘patient voice’: patients who experience antidepressant withdrawal symptoms are often dismissed, or misdiagnosed with relapse, or a new medical condition

“…It is noteworthy that although these drugs have different pharmacological mechanisms of action, the withdrawal symptoms from both benzodiazepine and antidepressants are phenomenologically remarkably similar, 67 although there are distinctions between them. 6 A portion of patients captured in this cohort were from countries outside the UK and therefore have given accounts of medical systems that are different from the NHS. However, the majority of respondents who reported country of origin were from the UK meaning lessons can be taken from this survey to apply to the NHS, reflected in the designation of 'high confidence' in this evidence by the National Guideline Centre.…”

“…recognition of the problems faced by patients withdrawing from antidepressants. [3][4][5][6] Recent systematic reviews of withdrawal symptoms from antidepressants have drawn attention to the fact that withdrawal symptoms are more common, more severe and longer-lasting than previously supposed, 5,7,8 30 years after antidepressant withdrawal symptoms from the new generation antidepressants were first reported, 7 and 20 years after they were first demonstrated in a doubleblind, placebo-substitution randomised trial. 9 Despite heated debate, there is general consensus that withdrawal affects at least a third or a half of patients stopping antidepressants 5,10 ; evidence indicates that this is likely to be less common for short term users, 11 and more common for longterm users.…”

May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance

“…40,45 Symptoms typically begin within 3 days of stopping antidepressant medication or initiating medication taper. Untreated symptoms may be mild and resolve spontaneously in 1-3 weeks; in other cases they may persist for months or even years, [40][41][42][43][44][45] leading to what has been defined as persistent post-withdrawal disorder. 41,45 Discontinuation of antidepressant medications may also trigger hypomania or mania, despite concurrent mood-stabilizing treatment.…”

“…Untreated symptoms may be mild and resolve spontaneously in 1-3 weeks; in other cases they may persist for months or even years, [40][41][42][43][44][45] leading to what has been defined as persistent post-withdrawal disorder. 41,45 Discontinuation of antidepressant medications may also trigger hypomania or mania, despite concurrent mood-stabilizing treatment. 47 The syndrome has a very variable course: it may be self-limiting, or may abate when AD are started again, or may require specific anti-manic treatment.…”