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...And Prevents the Pitfalls of Misdiagnosis

Antidepressant discontinuation symptoms can be misinterpreted as:^[1]

• recurrence of depression in a patient who stops his/her antidepressant therapy following remission of the original illness
• evidence that an antidepressant is ineffective in a patient who fails to comply with his/her therapy
• adverse effects of a new antidepressant following switching from 1 antidepressant to another.

In all of these cases, subsequent decisions about investigation, referral and treatment are likely to be inappropriate, may lead to a waste of resources, and can contribute to an incorrect and more negative prognosis.^[1]

Figure 1. Data from an analysis of UK spontaneous adverse reaction (ADR) reports of selective serotonin reuptake inhibitors (to March 1993) showing the number of discontinuation reactions per 1000 prescriptions.^[8]

Compliance May Suffer in Affected Patients

It is not uncommon for patients to miss antidepressant doses for several days. Such discontinuations would be expected to produce symptoms, which can develop within hours of missing a single dose of some agents. A compliance problem can then arise if the patient links his/her symptoms to the antidepressant without understanding the mechanism for development of symptoms, and particularly when the patient considers these symptoms to be evidence of 'addiction' to the antidepressant. In this way, discontinuation symptoms can result from, and cause, poor compliance.^[1]

Tapering May Prevent Symptoms...

Various case reports have shown that discontinuation symptoms can be suppressed by re-introduction of the antidepressant, with subsequent tapering preventing their re-emergence. Such findings support the conventional recommendation that discontinuation of antidepressants should be tapered as a matter of routine.^[1]

...But is More an Art Than a Science

Unfortunately, there are no controlled data demonstrating the effectiveness of tapering in general or of any tapering regimen in particular. According to the British National Formulary, antidepressants administered for 8 weeks or more should be reduced over a 4-week period.[9] Other authorities suggest reducing treatment dosage by one-quarter every 4 to 6 weeks after maintenance treatment. Another approach with SSRIs is to halve the dose and administer the drug on alternate days.^[1]

A number of specific factors will also influence tapering strategies. These include:

• the antidepressant used. Fluoxetine, for example, rarely causes discontinuation symptoms[6,8] and accordingly may not need to be tapered as a matter of routine.^[6,8,10] Paroxetine^[6,8] and venlafaxine,[5] in contrast, are much more likely to be associated with discontinuation symptoms and should therefore be tapered. Careful tapering is also required when stopping MAOIs, which can cause very severe discontinuation symptoms^[1]
• duration of therapy. Discontinuation symptoms are more likely in patients who have received more prolonged periods of therapy. Indeed, there is probably no need for tapering in patients who have received antidepressants for short periods^[1]
• previous history of discontinuation symptoms. Patients who have previously experienced discontinuation symptoms may require very gradual tapering.^[1]

Fluoxetine May Help

Anecdotal reports suggest that fluoxetine, at least in some cases, can suppress discontinuation symptoms associated with other SSRIs and venlafaxine. When successful in this regard, fluoxetine can then generally be stopped without re-emergence of symptoms.^[1]

Switching Therapies is a Special Case

Education of Both Patients and Doctors Needed

Current evidence suggests that substantial proportions of general practitioners, psychiatrists and pharmacists are unfamiliar with antidepressant discontinuation syndromes. In addition, patients are generally unaware that antidepressants are not addictive, that abrupt stoppage of antidepressants (because of noncompliance or when starting drug holidays to reduce adverse effects) can cause discontinuation symptoms, and that tapering of antidepressants is recommended to avoid such symptoms.^[1]

Flexible Approach to Treatment Required

Patients with discontinuation symptoms who remain depressed (e.g. treatment noncompliers) and those who are at high risk of relapse/recurrence should be recommenced on their antidepressant. In other cases, the severity of the discontinuation syndrome should determine treatment. Most patients will have mild reactions and need to be reassured only. Symptoms of moderate severity may require symptomatic treatment (e.g. short course benzodiazepines for insomnia). Severe or treatment-refractory symptoms may require recommencement of the antidepressant and subsequent careful tapering. Antipsychotics and hospital admission may also be required in patients who develop severe mania, confusion or psychotic symptoms.^[1]

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Reviewed: 12/2001