Depression sufficient to warrant professional care affects 2% to 4% of the general population. Cassem has observed that “92% of all persons suffering from it are either treated by nonpsychiatric personnel or are not treated at all”. Tricyclic antidepressants constitute the major form of treatment of depression. They are also used to treat various other conditions, such as phobias, obsessive-compulsive disorders, enuresis, sleep disorders (e.g., narcolepsy) and depressive equivalents (e.g., chronic pain). Their quinidine-like properties may soon prompt the use of these drugs as antiarrhythmic agents.

Side effects of tricyclic antidepressants are well known; these include dry mouth, blurred vision, constipation, reduced sweating, urinary retention, tachycardia, prostatism, raised intraocular tension in narrow-angle glaucoma, and toxic atropine-like effects on the central nervous system (e.g., delirium). Mentioned less often are the withdrawal symptoms, including nausea, vomiting, diaphoresis, restlessness, insomnia, headaches, dizziness, coryza, chills, gooseflesh, weakness, fatigue, musculoskeletal pain, abdominal cramps, malaise, anxiety, irritability, electrocardiogram changes, an akathisia-like syndrome and delirium. Similar symptoms are also reported when antipsychotic agents with potent antimuscarinic effects are suddenly discontinued. These symptoms are probably due to cholinergic rebound. Antipsychotic agents inhibit the metabolism of tricyclic antidepressants, so that the plasma levels of the drugs rise. Hence, withdrawal symptoms are more likely when combinations of these drugs are abruptly discontinued.

These symptoms have been reported with the most common tricyclic antidepressants in use — imipramine, amitriptyline and doxepin. They can occur with cessation of low doses, as in the case of a 29-year-old woman whose dose of amitriptyline was being tapered after 1 year of treatment; she had insomnia, anxiety, excessive sweating and abdominal cramps for 2 nights. They can also occur after a single dose is missed during active treatment. A 28-year-old woman who was depressed had been taking doxepin (25 mg three times a day) for about 28 days; nausea, restlessness and insomnia developed when she missed a single night’s dose. These symptoms can also occur following withdrawal from an overdose. A 29-year-old woman who had received treatment for an amitriptyline overdose complained of insomnia, restlessness, nausea, vomiting, excessive sweating, abdominal cramps and tension in the back of her head, all lasting for 2 days.

These withdrawal symptoms usually last about 48 hours and then, if the tricyclic antidepressant is not reinstated, will spontaneously remit.

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