Tricyclic antidepressants withdrawal

Maxmen and Ward (1995) provided an extensive list of tricyclic antidepressant withdrawal symptoms. One group of withdrawal symptoms includes a flulike syndrome without fever anorexia, nausea, vomiting, diarrhea, queasy stomach, and cramps. A second group involves sleep disturbances insomnia, hypersomnia, excessive dreaming, and nightmares. A third group includes mania and hypomania. Maxmen and Ward pointed out that these symptoms can also be experienced between doses as the blood level drops. 

When tricyclic antidepressants are withdrawn during pregnancy, they should be tapered gradually to avoid withdrawal symptoms. If possible, drug tapering is usually begun 5 to 10 days before the estimated date of confinement. 

Desipramine has been used to facilitate withdrawal from chronic PCP use. The rationale is that PCP depletes norepinephrine concentrations in brain, and that this tricyclic antidepressant is the most selective blocker of norepinephrine uptake. Consequently, some of the deficiency of the neurotransmitter could be remedied. A dose of 25 to 50 mg was said to reduce craving for several hours. Six of eight patients treated with this drug were successfully withdrawn, while none of the eight offered other types of programs were successful (45). 

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

Tricyclic antidepressants also have a documented syndrome associated with withdrawal from medications (Petti and Law, 1981). This syndrome can mimic appendicitis or the flu, and can include such symptoms as nausea and vomiting, headache, lethargy, and abdominal pain. If a child on TCAs presents with withdrawal symptoms, questions of compliance must be addressed. 

Despite these design flaws, many of the studies support the beneficial effects of tricyclic antidepressants in the treatment of depression associated with alcohol withdrawal. These benefits, however, do not exceed those of placebo after 3 weeks, and thus may have only limited application in actual clinical practice. 

Desipramine is a tricyclic antidepressant that has been tested in several double-blind trials among cocaine addicts. Like cocaine, desipramine inhibits monoamine neurotransmitter reuptake, but its principal effects are on norepinephrine reuptake. It was hypothesized that desipramine could relieve some of the withdrawal symptoms of cocaine dependence and reduce the desire for cocaine during the vulnerable period following cessation of cocaine. This drug showed efficacy early in the epidemic in a group of patients who were primarily white collar intranasal cocaine users. The majority of subsequent studies of desipramine-using, more severely ill cocaine addicts have been negative. 

Among the many toxicants that cause convulsions are chlorinated hydrocarbons, amphetamines, lead, organophosphates, and strychnine. There are several levels of coma, the term used to describe a lowered level of consciousness. At level 0, the subject may be awakened and will respond to questions. At level 1, withdrawal from painful stimuli is observed and all reflexes function. A subject at level 2 does not withdraw from painful stimuli, although most reflexes still function. Levels 3 and 4 are characterized by the absence of reflexes at level 4, respiratory action is depressed and the cardiovascular system fails. Among the many toxicants that cause coma are narcotic analgesics, alcohols, organophosphates, carbamates, lead, hydrocarbons, hydrogen sulfide, benzodiazepines, tricyclic antidepressants, isoniazid, phenothiazines, and opiates. 

The older tricyclic antidepressants and monoamine oxidase inhibitors also cause withdrawal mania and a variety of other adverse withdrawal effects, including cognitive and emotional disturbances and psychosis. Many of them have strong anticholinergic effects and therefore produce severe anticholinergic rebound on withdrawal, including cardiovascular and gastrointestinal symptoms. I have seen patients who have taken tricyclics for many years and then been unable to withdraw from them. 

Tricyclic antidepressants commonly produce withdrawal, frequently in the form of cholinergic rebound, with flulike symptoms such as nausea and vomiting, diarrhea, muscle aches, headache, fatigue, and anxiety (Breggin, 1991b). McMahon (1986) summarized ... 

Another unusual disturbance of hearing has been reported in a child taking tricyclic antidepressants (93). Auditory acuity was normal, but discriminative ability for both clear and distorted speech was depressed. The disorder cleared within some days of withdrawal. 

Two cases of non-thrombocytopenic purpura occurred in patients taking tricyclic antidepressants. Both improved on withdrawal (107). True thrombocytopenia, with platelets counts as low as 120 x 1012/1, occurred in a 79-year-old woman taking doxepin. During later treatment with amitriptyline, thrombocytopenia recurred, but not when she took imipramine (108). Cross-sensitivity must be highly specific to chemical structure, doxepin and amitriptyline being more like each other than imipramine. 

There is compelling evidence for a withdrawal syndrome due to abrupt discontinuation of tricyclic antidepressants (SEDA-5,16), and the literature has been reviewed (121). Reports have involved both imipramine and doxepin (122). Symptoms occur as early as the morning after a missed dose (123), but more often after 48 hours and up to 2 weeks after withdrawal. They include anxiety, restlessness, sweating, diarrhea, hot or cold flushes, and piloerec-tion. Amitriptyline withdrawal was followed by similar physical symptoms 36 hours after the last dose, followed by severe depressive illness (SEDA-17,18). 

There is clearly a need for larger controlled studies to determine the incidence and severity of withdrawal effects after withdrawal of tricyclic antidepressants. Based on uncontrolled observations, it has been suggested that the incidence varies from under a quarter to over half of all patients. 

A report of three cases (126) has suggested that central cholinergic overactivity is implicated, and that atropine sulfate 3 mg/day or synthetic anticholinergic agents (such as benzatropine mesylate 4 mg/day) ameliorate withdrawal symptoms within a few hours. The authors suggested that this technique may be especially useful in patients in whom tricyclic antidepressants must be abruptly withdrawn because of allergic or idiosyncratic reactions. 

In 190 patients taking tricyclic antidepressants that could not be discontinued before surgery, who underwent general and 61 local or regional anesthesia, there were no changes in the cardiovascular effect of halothane, induction time with pentobarbital, propanidid, or ketamine, or the duration of depolarization or recovery time (160). The general conclusion was that it is safer to continue treatment with tricyclic antidepressants than to risk potential disruption from withdrawal before surgery. 

Mirin SM, Schatzberg AF, Creasey DE. Hypomania and mania after withdrawal of tricyclic antidepressants. Am J Psychiatry 1981 138(l) 87-9. 

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