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Treating Depressive Disorders
 

DISCONTINUATION OF ANTIDEPRESSANT TREATMENT

Termination of antidepressant therapy is an area that has received significantly less attention than diagnosis and treatment.

Discontinuation
When patients stop long-term therapy with antidepressants, discontinuation symptoms frequently occur. Symptoms are more likely to occur in patients who abruptly stop antidepressant treatment as opposed to those whose treatment is gradually tapered.

Discontinuation symptoms can be mistaken for physical illness or relapse into depression. Symptoms can occur when compliance with treatment is intermittent (i.e., frequent missed doses), when medication is stopped abruptly, and less often, when dosage has been reduced. It is reasonable to ask patients who have been doing well on SSRI treatment and who suddenly develop new symptoms. These symptoms may include dizziness, nausea and vomiting, sensory and sleep disturbances, flu-like symptoms, anxiety, agitation or crying spells, if they might have left their medication at home while on a recent trip, for example, or have missed more than a few doses for any reason.

Discontinuation or Relapse?
Symptoms of discontinuation can be distinguished from symptoms of relapse of depression by time frame; discontinuation symptoms usually begin within 1 to 3 days of stopping medication, while relapse symptoms take 2 to 3 weeks to appear. In addition, discontinuation symptoms remit quickly after reinstitution of medication.

Depending on both the class of antidepressant and the individual drug, symptoms can range in severity and nature from mild and transitory to relatively incapacitating. Withdrawal effects can be related to the half-life of the antidepressant; faster onset occurs in drugs with shorter half-lives.

 

Discontinuation Symptoms, Prevention and Management
Discontinuation symptoms can be classified into four categories:

• gastrointestinal and somatic symptoms
• central nervous system symptoms
• sleep disturbances
• neurological symptoms

 

 

 

 

Prevention and management of discontinuation:

• reinforce with the patient the importance of compliance with medication dosage and schedule
• at completion of successful treatment, taper medication slowly (except fluoxetine) to the minimum therapeutic dose or below. A standardized tapering regimen should be instituted with any medication to avoid discontinuation syndrome.
• if symptoms are mild, reassure patient that symptoms will be short-lived
• if symptoms are severe, reinstitute dosage and slow rate of taper or treat with an extended half-life medication (such as fluoxetine). Discontinuation effects can generally be treated by reintroducing the same medication, or of one that is pharmacologically similar, and tapering at a more gradual rate, recommended at 25% per week.

 

 

 

 

 

 

 

 

 

A review of discontinuation symptoms by drug class follows:

Selective Serotonin Reuptake Inhibitors
Discontinuation symptoms occur in about one-third of patients who have been taking an SSRI, although rarely in patients who have received fewer than 7 weeks of treatment. Symptoms are more likely to occur with the shorter-acting SSRIs such as paroxetine, sertraline and fluvoxamine than with fluoxetine, which has an extended half-life. Usually, symptoms start within 24 to 72 hours of the last dose, and last from 7 to 14 days. The most common symptoms, in decreasing order of frequency, are dizziness, nausea, lethargy and headache.

Other common symptoms include anxiety, irritability, confusion, tremor, sweating, insomnia and memory problems. Paresthesia (burning, tingling or electric shock-like sensations), along with crying spells, have been reported as well.

Paroxetine: It is recommended that the dose be reduced by 5 mg/week for a period of several weeks to avoid withdrawal symptoms.

Venlafaxine: As an inhibitor of both noradrenaline and serotonin reuptake, discontinuation of higher-dose venlafaxine has been reported to cause insomnia, headaches and fatigue in some patients. Isolated case reports describe discontinuation symptoms that are similar to those reported for SSRI discontinuation and include dizziness, headache, nausea, fatigue and excessive dreaming.

 

Tricyclic Antidepressants
Symptoms that may result after either abrupt or gradual discontinuation of TCAs include:

• nausea, vomiting, diarrhea, headache, fatigue, malaise and generally flu-like symptoms
• insomnia, increased dreaming and other sleep disturbances
• movement disorders
• mania and hypomania.

 

 

 

 

 

Signs of withdrawal usually develop 24 to 48 hours after the last dose, although they may occur as early as 12 hours after a missed dose. Discontinuation symptoms may last as long as 1 month.

To avoid potential withdrawal symptoms, gradual tapering of TCAs over at least a 4-week period is recommended. If withdrawal symptoms persist, reintroducing the TCA, followed by a slower taper regimen and/or treatment with an anticholinergic agent are also recommended.

Monoamine Oxidase Inhibitors
Symptoms of MAOI discontinuation can be particularly severe and include delirium, thought disorganization, depression associated with cognitive impairment, mania, hypomania, aggressiveness, irritability, agitation, insomnia and myoclonic jerks.

Please see:

Section V: "Specific Pharmacological Issues"
CANMAT – Guidelines for the Diagnosis and Pharmacological Treatment of Depression
(1st Edition Rev., 1999)
P. 59

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Over one million Canadians suffer from some form of depressive illness.