Antidepressants withdrawal syndromes

Dilsaver SC. Antidepressant withdrawal syndromes phenomenology and pathophysiology. Acta Psychiatr Scand 1989 79(2) 113-7. 

Several natural products have been evaluated in rodent models of nicotine withdrawal. An extract of Hypericum perforatum (St. John s Wort, a putative antidepressant, and inhibitor of serotonin reuptake) reversed somatically expressed withdrawal behaviors and locomotor depression in spontaneous withdrawal (Catania et al. 2003). A benzoflavone compound isolated from Passiflora incarnata, interfered with the induction of physical dependence. Coadministration with chronic nicotine prevented various subsequent indicators of withdrawal syndrome in the mouse, including jumping, locomotor inactivity, immobility in the swim test and naloxone-precipitated escape jumping (Dhawan et al. 2002). 

Antidepressants differ from benzodiazepines in the onset and course of their actions (Fig. 2). Most cause an increase in anxiety on initiation of therapy, and anxiolytic effects occur later. In comparative studies, improvement matches that on benzodiazepines after 4 weeks (Rocca et al. 1997). Withdrawal effects, particularly rebound, are less problematic with antidepressants, although stopping treatment is associated with a significant rate of relapse, and a withdrawal syndrome has been described for most of the shorter-acting drugs. 

If an antidepressant is withdrawn during pregnancy, it should be gradually tapered to avoid maternal or fetal withdrawal syndromes. 

The experience of pregnancy itself is often anxiety provoking, and symptoms sufficient to warrant drug therapy are common in this group ( 16). Although this discussion primarily focuses on the benzodiazepines (BZDs), antidepressants and buspirone may also be used for women of childbearing age with certain anxiety-related disorders. Perhaps the best-documented adverse effect of the BZDs is a neonatal withdrawal syndrome, which has been reported to occur with several of the agents (e.g., diazepam, alprazolam, and triazolam). In addition, there is a weak positive relationship between diazepam exposure and oral clefts ( 17). 

Other indications for the use of antipsychotics include Tourette s syndrome, disturbed behavior in patients with Alzheimer s disease, and, with antidepressants, psychotic depression. Antipsychotics are not indicated for the treatment of various withdrawal syndromes, eg, opioid withdrawal. In small doses, antipsychotic drugs have been promoted (wrongly) for the relief of anxiety associated with minor emotional disorders. The antianxiety sedatives (see Chapter 22) are preferred in terms of both safety and acceptability to patients. 

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. 

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). 

A Pu. 70% protein bound, half-life = 11 hrs. More rapid onset than tricyclic antidepressants. Some argue that Alprazolam has high dependency/abuse potential and a severe withdrawal syndrome. Few interactions. Additive with other CNS depressants. ... 

Opioids (especially methadone and heroin) are the most common cause of serious neonatal drug withdrawal symptoms. Other dmgs for which a withdrawal syndrome has been reported include phencyclidine (POP), cocaine, amphetamines, tricyclic antidepressants, phenothiazines, benzodiazepines, barbiturates, ethanol, clonidine, diphenhydramine, lithium, meprobamate, and theophylline. A careful dmg history from the mother should include illicit drugs, alcohol, and prescription and over-the-counter medications, and whether she is breast-feeding. 

Fetotoxicity There have been reports of neonatal withdrawal symptoms with SSRIs, but httle is known of this phenomenon with other antidepressants. When seven mother-child pairs exposed to venlafaxine from the second trimester were studied p "], five of the neonates had a withdrawal syndrome, including tachypnea and respiratory distress the changes corresponded to falling plasma venlafaxine concentrations. The neonate exposed to the highest maternal dose of venlafaxine (300 mg/day) had the most severe and most persistent signs. 

Nervous system Seizures have been attributed to flumazenil [104, 105, 106, 107, 108, 109, 110, 111 ], including status epilepticus [112, 113 ], which can be fatal. However, it has been suggested that seizures are not a toxic effect of flumazenil, but are in many cases instead due to unmasking of the anticonvulsant effect of the benzodiazepine or to a severe benzodiazepine-withdrawal syndrome furthermore, in some cases they may be due to other drugs taken at the same time, such as tricyclic antidepressants [1143]. Thus, it has been recommended that flumazenil should not be given to patients who have used benzodiazepines for seizure disorders or to patients who have taken other drugs that increase the risk of seizures (e.g. bupropion, ciclosporin, cocaine, cyclic antidepressants, isoniazid, lithium, methylxanthines, monoamine oxidase inhibitors, and propoxyphene). 

As was previously mentioned, a hangover-like syndrome is common the next day after use of MDMA. MDMA withdrawal, which is thought to be caused by serotonin depletion, can last for weeks and includes symptoms of depression, anxiety, restlessness, and insomnia (Allen et al. 1993 McGuite et al. 1994). No specific treatments are currently indicated fot this withdtawal syndrome, although the antidepressant bupropion may be helpful (Solhkhah... 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

In general, the lowest effective dose of the drug should be used, particularly in elderly patients. Dose titration should be undertaken slowly. Similarly, on discontinuation of a drug, the dose should be reduced slowly, the rate of decrease being decided by the elimination half-life of the drug. Some psychotropic drugs produce a discontinuation syndrome that can usually be avoided by slow withdrawal. In particular, sedatives, anxiolytics and antidepressants can cause withdrawal effects. 

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. 

There is a clinical impression that psychostimulants may be helpful in HIV- or AIDS-related affective syndromes (487, 488). Thus, methylphenidate 10 to 20 mg per day (up to 40 mg per day) or dextroamphetamine 5 to 15 mg per day (up to 60 mg per day) has been helpful in patients with mild depression who also show symptoms of social withdrawal, fatigue, and apathy, as well as mild cognitive impairment. At times, the combination of low-dose antidepressant and psychostimulant may be more effective and less likely to induce adverse CNS effects. 

McMahon, T. C. (1986). A clinical overview of syndromes following withdrawal from antidepressants. Hospital and Community Psychiatry, 37, 883-884. 

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