Tricyclic antidepressants discontinuation

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

MAOIs should not be administered together with or immediately following tricyclic antidepressants (TCAs). At least 14 days should elapse between the discontinuation of the MAOIs and the institution of a TCA. Some TCAs have been used safely and successfully in combination with MAOIs. 

Coadministration of beta-blockers can potentiate rebound hypertension upon discontinuation of medications, and it is therefore recommended that the beta-blocker be withdrawn before the tt2 agonist (Physicians Desk Reference, 2001). Tricyclic antidepressants may also produce changes in sinus node and AV conduction, and it is recommended that they be used cautiously in combination with tt2 agonists (Physicians Desk Reference, 2001). However, in child psychiatric practice, there has been debate about whether there are adverse interactions related to concomitant use of tricyclics and tt2 agonists. Finally, the tt2 agonists may potentiate the effects of CNS depressants (e.g., barbiturates) or other medications that produce sedation, so lower doses of each may be warranted. 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

Anderson DN, Wilkinson AM, Abou-Saleh MT, et al Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetra-hydrobiopterin-dependent hydroxylation. Acta Psychiatr Scand 90 10-13, 1994 Anderson IM, Cowen PJ Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers. Psychopharmacology 106 428-432, 1992 Anderson IM, Tomenson BM Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants a meta-analysis. BMJ 310 1433-1438, 1995... 

Levodopa or dopamine agonists produce diverse dyskinesias as a dose-related phenomenon in patients with Parkinson s disease dose reduction reverses them. Chorea may also develop in patients receiving phenytoin, carbamazepine, amphetamines, lithium, and oral contraceptives, and it resolves with discontinuance of the offending medication. Dystonia has resulted from administration of dopaminergic agents, lithium, serotonin reuptake inhibitors, carbamazepine, and metoclopramide and postural tremor from theophylline, caffeine, lithium, valproic acid, thyroid hormone, tricyclic antidepressants, and isoproterenol. 

Plasma levels of doxepin similar to those achieved during oral therapy may be obtained with topical application the usual drug interactions associated with tricyclic antidepressants may occur. Therefore, monoamine oxidase inhibitors must be discontinued at least 2 weeks prior to the initiation of doxepin cream. Topical application of the cream should be performed four times daily for up to 8 days of therapy. The safety and efficacy of chronic dosing has not been established. Adverse local effects include marked burning and stinging of the treatment site which may necessitate discontinuation of the cream in some patients. Allergic contact dermatitis appears to be frequent, and patients should be monitored for symptoms of hypersensitivity. 

The efficacy of imipramine has been repeatedly demonstrated in controlled trials about 85% of children treated within a week of the start of medication, but tolerance frequently develops after a number of weeks and relapse is high after discontinuation of the treatment. Relatively low doses of imipramine only are needed, but the typical side effects of tricyclic antidepressants limit the prolonged use of the drug. The mechanism of action of imipramine in the treatment of nocturnal enuresis is unclear but one possible action is through a direct anticholinergic action on the bladder wall. 

Discontinuing selective serotonin reuptake inhibitors (SSRIs) may induce a syndrome wherein the main neuropsychiatric symptoms are dizziness, shock-like sensations, anxiety, irritability, agitation, and insomnia. These symptoms usually develop 1 to 7 days after abrupt or gradual discontinuation. Antidepressant discontinuation may also induce mania, mainly reported with tricyclics and monoamine oxidase inhibitors but also observed with SSRIs. 

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). 

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. 

Charney DS, Heninger GR, Sternberg DE, Landis H. Abrupt discontinuation of tricyclic antidepressant drugs evidence for noradrenergic hyperactivity. Br J Psychiatry 1982 141 377-86. 

MAO Inhibitors and Other Antidepressants. Product literature and case reports caution against concurrent use of MAO inhibitors with tricyclic antidepressants (e.g., amitriptyline, imipramine) because severe atropinelike reactions, tremors, convulsions, hypothermia, and vascular collapse can occur. The labeling for most of these products warns that therapy with a MAO inhibitor or a tricyclic antidepressant should not be initiated until at least 7-14 days after therapy with the other drug has been discontinued. 

Discontinuance syndrome—response to stopping or interrupting medication treatment. Examples are narcotic withdrawal or "cholinergic rebound" when tricyclic antidepressants or antipsychotics are abruptly stopped. 

History of bone marrow depression hypersensitivity to carbamazepine and tricyclic antidepressants concomitant use of monoamine oxidase (MAO) inhibitors. Discontinue MAO inhibitors for 2 14 days before carbamazepine administration. 

BPH symptoms may be caused by medications, including antihistamines, phenothiazines, tricyclic antidepressants, or anticholinergic agents. In this case discontinuing the causative agent can ameliorate symptoms. 

Occasional Confusion amnesia disinhibition paradoxical excitement depression dizziness witiidrawal symptoms, including convulsions, on abrupt discontinuance (witiidrawal may be especially difficult with alprazolam) rebound insomnia or excitement Rare Hypotension blood dyscrasias jaundice allergic reactions paradoxical rage reactions stuttering with alprazolam BUPROPION, Anxiety agitation insomnia tremor anorexia BUSPIRONE, Dizziness headache nausea paresthesias diarrhea CHLORDIAZEPOXIDE, see Benzodiazepines CHLORPROMAZINE, see Phenothiazines, aliphatic CHLORPROTHIXENE, similar to Phenothiazines CLOMIPRAMINE, see Tricyclic antidepressants CLORAZEPATE, see Benzodiazepines CLOZAPINE... 

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