Extended antidepressant maintenance and discontinuation syndromes

Abstract

Unipolar and bipolar depression are episodic, recurrent illnesses for the majority of patients. Because each episode engenders considerable costs for patients, families, and society, prevention of recurrences has high priority. Numerous studies demonstrate that maintenance antidepressants or mood stabilizing medications are efficacious in preventing recurrences. A review of maintenance studies supports the view that all antidepressants perform significantly better than placebo in preventing recurrences of depression—with the stipulation that full antidepressant doses be employed. Earliest studies, conducted two decades ago, evaluated tricyclics (TCAs), heterocyclics, and lithium, while recent studies have focused on selective serotonin reuptake inhibitors (SSRIs). Compliance is essential. Strategies for enhancing compliance include selection of medications with reported safety and few side effects, education of patients and families, referral to patient advocacy groups, and use of new technological compliance aids. Preliminary data suggest that SSRIs are better tolerated than TCAs; fewer patients discontinue these agents due to side effects. Selection criteria for maintenance treatment have not been well determined, but three or more prior episodes is recognized as a relatively strong indicator. Other clinical or genetic criteria have also been suggested. For various reasons, patients may discontinue medications, and when this happens withdrawal phenomena may occur. Withdrawal effects are well documented for all antidepressants and can be profound with TCAs. After stopping some SSRIs, a few withdrawal symptoms may have similarities with those following discontinuation of TCAs, but unique “CNS‐like” effects are frequently described, including brief recurrent episodes of dizziness, lightheadedness, vertigo, electric shock‐like sensations, and gait instability. These appear to be half‐life dependent, with agents with shorter half‐lives having more discontinuation symptoms. If antidepressant medications must be discontinued, a gradual taper is preferable, perhaps extending three to six months or longer to prevent discontinuation effects, enable adaptation at the receptor level and allow earlier recognition and treatment of recurrent depressive symptoms. Depression and Anxiety, Volume 8, Supplement 1:43–53, 1998. © 1998 Wiley‐Liss, Inc.

Guidance for the Discontinuation or Switching of Antidepressant Therapies in Adults

“…3,28 Some authors propose tapers as long as 6 to 12 months when complete DC of the agent is desired to allow the receptors to adapt and for earlier detection of recurrent depression symptoms. 4,32 Additionally, for certain agents (eg, irreversible MAOIs), the pharmacodynamic duration of activity may be equally important to consider and more reflective of the offset of activity than drug t 1/2 . To prevent withdrawal, it is generally acceptable to reduce the dose by 25% per week until DC of the medication.…”

“…1 Studies have been conducted to determine the best methods to decrease the incidence of AD withdrawal and have yielded conflicting results. 1 –4 To date, there are no complete guidelines that give guidance on the DC or switching of ADs. The package inserts for these medications usually provide vague and nonspecific recommendations, stating that withdrawal is a potential risk, to taper the medication instead of abruptly discontinuing it and to monitor the patient for any signs of withdrawal.…”

The application of knowledge discovery in databases to post‐marketing drug safety: example of the WHO database

“…Spontaneous reporting systems are non-interventional with respect to prescribing habits and thus reporting can occur of events that cannot be readily studied for ethical reasons, such as overdoses or inappropriate co-medication. High-quality reports of hitherto unsuspected reactions have led to the detection of signals such as SSRI-electric shock syndrome [8][9][10], and sumatriptanpain activation [11] which would have been hard to detect otherwise. A good understanding of the nature of spontaneous reports is critical to the effective use of KDD tools.…”

Clinical effectiveness and cost-consequences of selective serotonin reuptake inhibitors in the treatment of sex offenders

“…Studies designed to assess discontinuation syndromes with SSRIs reported rates of about 20% or more. 42,43 Typically, symptoms begin within 24-72 hours of stopping the treatment and last 1-2 weeks, but occasionally much longer. 44 The most commonly reported symptoms were anxiety, paraesthesia, shock-like sensation, balance problems, tremor, seating, insomnia and nightmares.…”