Relatively large doses of psychoactive agents have been associated with the occurrence of sudden death in primates.'\" Both therapeutic and toxic doses of psychoactive agents have been associated with a number of cases of ventricular arrhythmias and sudden death in patients.4-I0 Cases of sudden death have been recorded that were caused by cardiac toxicity after administration of large doses of thiorida~ine.4*~.~ Other cases of sudden death associated with the use of chlorpromazine, thioridazine, and other phenothiazines at therapeutic doses have been reported as we11.6.8.10 In fact, Leestma and Koeni$ found 58 cases of sudden or unexplained death involving phenothiazine drugs when they reviewed the literature. Sudden death has also been reported after an apparent recovery from phenothiazine overdose.\" The use of tricyclic antidepressant agents in both therapeutic10 and toxic7 doses has also been reported to be associated with cardiotoxicity.12-16 Studies involving the administration of amitriptyline12J3J7 or imipramineI8 to psychiatric patients with cardiac disease have shown a greater incidence of sudden death in patients administered these agents when compared with patients in a control group matched for age, sex, diagnosis, and length of hospital stay. As sudden death linked with psychoactive drugs has

Cardiotoxicity of tricyclic antidepressants

Cardiac arrhythmia, sudden death, and psychoactive agents.

Background: Tianeptine is an atypical antidepressant marketed as Stablon since the late 1980’s. While chemically very similar to tricyclic antidepressants, tianeptine was thought to have the apparently paradoxical mechanism of action of enhancing serotonin reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AM-PA receptors) coupled with agonist effects at mu opioid receptors (-receptors). Objective: We have reviewed clinical and preclinical data for tianeptine to provide a compre-hensive study of its pharmacology. Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepres-sant treatments, with improved tolerability as it is significantly less prone to disrupting the patient's normal functionality. Tianeptine appears more efficacious in males than females, although these gender-specific differences may be accounted for by pharmacokinetics. Pre-clinical data suggest that the ability to stabilise glutamatergic neurotransmission may underlie tianeptine’s ability to improve cognitive function and anxiety-related symptoms. Alternative-ly, μ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fast-acting antidepressant. Agonist actions at μ-receptors could also explain the potential abuse li-ability and dependence issues seen with high dose tianeptine. Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental tool yielding valuable insights into the molecular mechanisms underlying depression.

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Cardiotoxicity of tricyclic antidepressants

Citations

Cardiac arrhythmia, sudden death, and psychoactive agents.

Tianeptine: An Atypical Antidepressant with Multimodal Pharmacology

Advances in Psychopharmacology

References

Cardiac arrhythmia, sudden death, and psychoactive agents.

Tianeptine: An Atypical Antidepressant with Multimodal Pharmacology

Advances in Psychopharmacology

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