Drug Interactions with Clomipramine (Anafranil)

Beaumont, G

doi:10.1177/030006057300100543

Cited by 44 publications

(12 citation statements)

References 18 publications

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“…The literature contains numerous reports of cases of serotonin syndrome secondary to the combination of an MAOI and a tricyclic antidepressant, 15,11,12,15,17,20,27,28,[67][68][69][70][71][72][73][74] Moclobemide is a reversible MAOI which is relatively selective for MAO-A. It was hoped that this drug would be less likely to be implicated in the serotonin syndrome, but one case was reported in association with a moclobemide/imipramine combination, [73] and a second following administration of moclobemide in combination with clomipramine,l27] The combination of an MAOI and tricyclic antidepressant causing serotonin syndrome is the only one that has been reported to cause seizures.…”

Section: Monoamine Oxidase Inhibitor (Maoi) and Tricyclic Antidepressmentioning

confidence: 99%

“…It was hoped that this drug would be less likely to be implicated in the serotonin syndrome, but one case was reported in association with a moclobemide/imipramine combination, [73] and a second following administration of moclobemide in combination with clomipramine,l27] The combination of an MAOI and tricyclic antidepressant causing serotonin syndrome is the only one that has been reported to cause seizures. [I2, 13,15,17,28] The simultaneous use of drugs from these 2 classes has been previously advocated and used successfully by some authors for the treatment of refractory depression, with reportedly few adverse effects; however, this combination should not be considered except in extreme circumstances. 175 ]…”

Section: Monoamine Oxidase Inhibitor (Maoi) and Tricyclic Antidepressmentioning

confidence: 99%

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The Serotonin Syndrome

Sporer

1995

Drug Safety

183

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The serotonin syndrome has increasingly been recognised in patients who have received combined serotonergic drugs. This syndrome is characterised by a constellation of symptoms (confusion, fever, shivering, diaphoresis, ataxia, hyperelflexia, myoclonus or diarrhoea) in the setting of the recent addition of a serotonergic agent. The most common drug combinations causing the serotonin syndrome are monoamine oxidase inhibitors (MAOIs) and serotonin selective reuptake inhibitors (SSRIs), MAOIs and tricyclic antidepressants, MAOIs and tryptophan, and MAOIs and pethidine (meperidine). This syndrome is caused by excess serotonin (5-hydroxytryptamine; 5-HT) availability in the CNS at the 5-HT1A-receptor. There may also be some interaction with dopamine and 5-HT2-receptors. This syndrome probably has a low incidence, even among patients taking these drug combinations, and there is likely to be some other as yet unidentified inciting factor causing some patients to develop a full serotonin syndrome. Because fatalities and severe complications have accompanied the serotonin syndrome, the previously described drug combinations should be used cautiously or not at all. The serotonin syndrome is usually mild and, if managed with drug withdrawal and supportive therapy, generally improves within hours. Patients who develop hyperthermia should be treated aggressively with external cooling and paralysis. Methysergide and cyproheptadine appear to be useful adjuncts in treating the serotonin syndrome.

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Section: Monoamine Oxidase Inhibitor (Maoi) and Tricyclic Antidepressmentioning

confidence: 99%

Section: Monoamine Oxidase Inhibitor (Maoi) and Tricyclic Antidepressmentioning

confidence: 99%

The Serotonin Syndrome

Sporer

1995

Drug Safety

183

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“…There may be increased pressor sensitivity to CNS stimulants after prior MAOI therapy, which can result in increases in blood pressure (Pettinger et al 1968). Concurrent therapy with stimulants and tricyclic antidepressants has been reported to enhance the cardiovascular effects of stimulants and increase the serum concentration of antidepressants, which may improve the clinical response to the antidepressant but may also increase the risk of toxicity (Beaumont 1973;Raisfeld 1972). The incidence of adverse effects in hyperactive patients has been studied in double-blind, placebo-controlled trials by Barkley et al (1990).…”

Section: Adverse Effects Profilementioning

confidence: 99%

Risks and Benefits of Drugs Used in the Management of the Hyperactive Child

Fox

Rieder

1993

Drug Safety

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Childhood hyperactivity is a common behavioural complaint. The therapeutic options for physicians caring for children with hyperactivity are considerable and varied; current recommendations call for a multidisciplinary approach, including when necessary the use of drug therapy. Central nervous system stimulants are the primary agents used in the therapy of hyperactivity. The majority of children with hyperactivity diagnosed using careful clinical criteria will demonstrate short term benefits in cognitive and behavioural terms, but long term efficacy remains controversial. There appears to be a subset of patients who do not demonstrate a beneficial response to stimulants, although there is controversy as to whether this may be dose dependent. The adverse effects of most concern are suppression of growth, the development of tics and the potential for abuse. Antidepressants and clonidine are useful agents for the therapy of patients resistant to stimulant therapy. Although the most frequent adverse events of antidepressant therapy are associated with the anticholinergic activity of these agents, the most common serious adverse events are associated with antidepressant overdose. Concern has been expressed because of case reports describing an association between antidepressant therapy for hyperactivity and sudden death. A number of other therapies have been used for hyperactivity. Although these therapies may be effective in subsets of patients with hyperactivity, there is little research detailing how to identify patients who might be expected to respond to such treatment.

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“…Although case reports of 5HT syndrome had been reported as early as the 1970s (Beaumont, 1973;Marley and Wozniak, 1984;Blackwell, 1991;Stern et al, 1992), there have been no systematic comparisons of patients treated with the combination of an MAO inhibitor plus CMI vs. an MAO inhibitor plus conventional TCA. The use of MAO inhibitor/CMI combination in the present report was undertaken before the extreme dangers of this drug combination were generally appreciated.…”

Section: Discussionmentioning

confidence: 99%

Clomipramine augmentation in treatment-resistant depression

1997

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In depression that is resistant to tricyclic antidepressant (TCA) therapy, the substitution of a selective serotonin re‐uptake inhibitor (SSRI), clomipramine, or a monoamine oxidase (MAO) inhibitor has been recommended. However, adding an additional antidepressant medication from a different drug class may produce even more rapid efficacy. In this regard, the combination of a MAO inhibitor or a SSRI plus a TCA has been shown to be of value in treatment‐resistant depression (TRD) In this report, we examined the efficacy of clomipramine augmentation in 20 patients who failed to respond to either a MAO inhibitor or fluoxetine therapy for at least a 6‐week period, and compared this to a third group given MAO inhibitor plus a conventional TCA Two out of 9 (22%) MAO inhibitor/clomipramine patients and 4 out of 11 (36%) fluoxetine/clomipramine patients improved (Fisher's Exact test, P = ns), compared to 3 out of 7 (43%) patients taking MAO inhibitor/TCA (P = ns). However, the MAO inhibitor/clomipramine group experienced significantly more adverse events which necessitated stopping treatment (56%) when compared to the fluoxetine/clomipramine (9%) and compared to the MAO inhibitor/TCA group (0%) (χ2 = 8.9, df = 2, P < 0.05). These adverse events included several cases of serotonin syndrome of mild to moderate severity. These observations indicate that clomipramine augmentation of a failed MAO inhibitor trial is of marginal efficacy (compared to augmentation with a conventional TCA) and should be employed with extreme caution. Depression and Anxiety 5:84–90, 1997. © 1997 Wiley‐Liss, Inc

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Drug Interactions with Clomipramine (Anafranil)

Cited by 44 publications

References 18 publications

The Serotonin Syndrome

The Serotonin Syndrome

Risks and Benefits of Drugs Used in the Management of the Hyperactive Child

Clomipramine augmentation in treatment-resistant depression

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