Tricyclic antidepressants long-term effects

The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake (see Figure 12.3). This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, H histaminic and a -adrenergic receptors. Compared with tricyclic antidepressants, the SSRIs cause fewer anticholinergic effects and lower cardiotoxicity. However, the newer serotonin reuptake inhibitors should be used cautiously until their long-term effects have been evaluated. 

Tricyclic antidepressants are not licensed for use in the anxiety disorders, so in theory the SSRIs should not be compared with them in cost-effectiveness terms. The SSRIs and venlafaxine are supplanting benzodiazepines as the latter s long-term problems become more appreciated. The SSRIs will take an increasing proportion of the market. However, in comparison with the overall costs of the anxiety disorders, this drug expenditure can be justified. Further cost-offset and cost-effectiveness studies will help hammer this point home. 

Virtually all types of drug that have been shown to be effective in major depression exert profound effects on the functioning of the serotoninergic or noradrenergic systems, or both. Although some treatments have been shown to decrease the sensitivity of certain postsynaptic 5-HT and NE receptors, it is generally believed that it is an enhancement of neurotransmission in these systems that is responsible for the improvement of the core symptoms of depression. For instance, long-term administration of tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) decreases the density of (3-adrenoceptors and cortical 5-HT2 receptors (Blier and Abbott 2003). 

Long-term efficacy and tolerability is of considerable clinical importance for any medication proposed for the treatment of panic disorder. Tricyclic antidepressants, in particular, are associated with side effects such a weight gain and anticholinergic effects, which may make them difficult for patients to tolerate long-term. 

Steiger A, Holsboer F, Benkert O Long-term studies on the effect of tricyclic antidepressants and selective MAO-A-inhibitors on sleep, nocturnal penile tumescence and hormonal secretion in normal controls, in Sleep 86. Edited by Koella WP. Stuttgart, Fischer Verlag, 1988, pp 335-337... 

Oral contraceptives reduce the clearance of imipramine, probably by reducing hepatic oxidation, and thus increase its half-life. Hydroxylation of amitriptyline is inhibited by contraceptive steroids. The clinical significance is uncertain, but there is at least anecdotal evidence of an increase in antidepressant adverse effects (360). Caution should be exercised when tricyclic antidepressants are used long term in women taking oral contraceptives. 

Long-term health effects from antidepressants include the increased risk of deliberate self-harm (DSH), which may occur more with the SRRIs than the tricyclic antidepressants. The self-harm may occur by overdosing with the prescribed drug, but is more frequently by other means. 

Treatment with antidepressants will affect a person s ability to drive or operate machinery. Among the tricyclic antidepressants, amitriptyline and doxepin impair skills compared with imipramine and nortriptyline. Fluoxetine and dothiepin also show similar effects, such as affecting ability to work. The United Kingdom s Medical Commission on Accident Prevention has recommended that patients on long-term psychotropic medication are unsuitable drivers of heavy vehicles or public transport services.132,133... 

Overall, amoxapine appears to have some advantage over other tricyclic antidepressants possible earlier onset of action and relative freedom from serious cardiotoxic effects. Its major drawbacks are the potential for neuroleptic adverse effects, a high incidence of seizures, deaths in overdose (2), and the possibility of long-term neurological damage. 

Tyrer P. Clinical effects of abrupt withdrawal from tricyclic antidepressants and monoamine oxidase inhibitors after long-term treatment. J Affect Disord 1984 6(l) l-7. 

---