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Adverse Drug Reactions Advisory Committee (ADRAC). 1996

Australian Adverse Drug Reactions Bulletin

Volume 15, Number 1, February 1996

SSRIs and withdrawal syndrome

Withdrawal syndromes have long been recognised with the opioids and benzodiazepines but are rarely reported with other drugs. Fluoxetine (Prozac), paroxetine (Aropax) and sertraline (Zoloft) are antidepressant drugs belonging to the class of selective serotonin reuptake inhibitors (SSRI's). To date the Committee has received 26 reports of withdrawal symptoms in connection with the use of these drugs as summarised in the table below.

The age (range 23 to 68 years) and sex distribution (23 females and 9 males) probably reflect usage. In those reports which included the information, duration of therapy ranged from several weeks to months and onset of the reaction was within the first week (usually in the first couple of days) after ceasing therapy. In 8 cases the symptoms abated on recommencing the drug but recurred in 3 of these after the drug was again stopped. One patient experienced withdrawal symptoms in connection with sertraline and later, also with paroxetine.

The symptoms most commonly reported on withdrawal were dizziness (15 reports) and nausea (10). Anxiety, headache (both 5 reports), agitation, insomnia, increased sweating, tremor and vertigo (4 of each), hallucinations, and depersonalisation (3 of each) were also described. There was a total of 51 different symptoms documented in the reports with a wide range of other neurological and psychiatric symptoms including amnesia, ataxia, blurred vision, confusion, dysarthria, delirium, fatigue, hyperacusis, hypertonia, meningism, mood swings, neurosis, nervousness, nightmares, paraesthesia, rigors, sensory disturbance, tinnitus, and twitching. There was also a report of a neonatal withdrawal reaction. Eighteen of the patients had recovered at the time of reporting and there were no fatalities.

Interestingly, paroxetine accounted for the majority of reports and its shorter elimination half-life in addition to the fact that it lacks active metabolites are possibly pertinent in this context. In contrast, fluoxetine has a longer half-life and its active metabolite, norfluoxetine has a half-life of 6-9 days.

Prescribers should be aware that drugs in this class have the potential to produce withdrawal symptoms if therapy is ceased abruptly. When a decision is made to terminate therapy, gradual reduction of the dose may be necessary particularly for drugs with a shorter elimination half-life.

Total Reports Reports of withdrawal (%) Daily dose (mg) Half-life

Fluoxetine 578 5 (0.5) 20-40 2-3 days

Paroxetine 406 22 (5.4) 20-40 ~1 day

Sertraline 242 7 (2.9) 50-100 26 hours