Side Effects of Antidepressant Drugs

Drugs Sedation Insomnia A. Tricyclic Effects Nausea antidepressants Hypotens 

Note 0 = no side effect + = minor side effect -H- = moderate side effect -m- = major side 

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These are uncommon side effects of antidepressant drugs, particularly when used at normal therapeutic doses. 

Side Effects of Antidepressant Drugs - Recent publications pertaining to the clinical side effects of antidepressant agents are by Hollister, Kahr et al. 5, Tschen et al. 6, Blair and Simpson and Simpson et al. 8. The toxicology of amitriptyline has been described by Myers et al. 9. 

Figure 2.1 Like nearly all antidepressant drugs, TCAs can have significant side effects. Some of those side effects for different TCAs are listed here, along with their frequency. Sexual dysfunction is a common side effect of antidepressant drugs and has a high probability of occurrence in patients who take the drugs listed here. The chances of agitation and insomnia, on the other hand, are quite low.

For people who are depressed, and especially for those who do not receive enough benefit from medication or for whom the side effects of antidepressants are troubling, the fact that placebos can duplicate much of the effects of antidepressants should be taken as good news. It means that there are other ways of alleviating depression. As we have seen, treatments like psychotherapy and physical exercise are at least as effective as antidepressant drugs and more effective than placebos. In particular, CBT has been shown to lower the risk of relapsing into depression for years after treatment has ended, making it particularly cost-effective. 

The side effects of antidepressants, sometimes very unpleasant, olten lead patients to interrupt their treatment or to reduce the drug dose, which involves a great risk in view of the high relapse rate and danger of suicide in depression. The newer antidepressants, such as trazodone, fluoxetine and other SSRIs and moclobemide, are characterized by better tolerability and lower toxicity and are therefore preferred in the treatment of outpatients and elderly patients (Rudorfer and Potter, 1989). A detailed list of general and specific common side effects associated with the newer generation of antidepressants is seen in Table 1.7. 

For patients who take antidepressants from these last two groups, TCM treatment should be applied according to careful syndrome differentiation, to remove the obstruction, harmonize the Qi and blood, and balance the Yin and Yang in order to prevent and reduce the side effects of the drugs. 

Baldwin D, Mayers A. Sexual side-effects of antidepressant and antipsychotic drugs. Adv Psychiatr Treat 2003 9 202-10. 

Several early studies suggest that tryptophan can potentiate the antidepressant effect of monoamine oxidase inhibitors. However, since it also tends to potentiate the side effects of these drugs, the combination is usually used only in treatment-resistant patients. Even though tryptophan potentiates the action of monoamine oxidase inhibitors, it does not seem to potentiate the action of other antidepressant treatments such as tricyclic antidepressant and electroconvulsive therapy.52... 

As a consequence, several drugs have been developed by enhancing the side effect of another drug. For example, the mood-improving effect of iproniazid was discovered when it was tested as an antituberculous drug antidepressant inhibitors of neurotransmitter reuptake, like imipramine and desipramine, stem from the antipsychotic dopamine antagonist chlorpromazine, which itself was derived from Hi antihistaminics [35,36,51]. 

Symptoms resolved within 48h of discontinuing cyclobenzaprine. Serotonin syndrome is a potential complication of initiating cyclobenzaprine, and when adding opiate or antidepressant medications to the regimen. Given its tricyclic properties, serotonin syndrome is a potential side effect of this drug. 

Another example of chiral switching is that of the selective serotonin reuptake inhibitor (SSRI) antidepressant Celexa, which was introduced to the market in 1998 by Forest Laboratories. Celexa is a racemic mixture of (i )-citalopram oxalate and (5)-citalopram oxalate. While orrly the (S) enantiomer has therapeutic antidepressant properties, both enantiomers contribute to the side effects of the drug and therefore limit effectiveness and patient tolerance. In 2002, the FDA approved Lexapro, a new antidepressant derived from Celexa but from which the therapeutically ineffective (R) enantiomer has been removed. The benefits of isolating the active isomer include smaller required dosages, reduced side effects, and a faster and better patient response to the drag. 

The side effects of these drugs are well known and have been summarized earlier (SED VIII, p. 313). Drugs with selective activity may be classified as antidepressants, antipsychotics, antihistamines, antispasmod-ics or antiparkinsonism agents and yet have anticholinergic actions as side effects. When two or more are given together the unwanted effects are more likely to arise. 

Many antihistamines, antipsychotics and antidepressants have stmctural similarities with muscarinic receptor antagonists and, predictably, show antimuscarinic effects which are considered in many cases the major side effects of these drug categories. Imipramine (Fig. 16.19) is a... 

The adverse side-effects of the TCAs, coupled with their toxicity in overdose, provoked a search for compounds which retained their monoamine uptake blocking activity but which lacked the side-effects arising from interactions with Hj, aj-adreno-ceptors and muscarinic receptors. One of the first compounds to emerge from this effort was iprindole, which has an indole nucleus (Fig. 20.3). This turned out to be an interesting compound because it has no apparent effects on monoamine uptake and is not a MAO inhibitor. This, together with its relatively minor antimuscarinic effects, led to it commonly being described as an atypical antidepressant. Mechanisms that could underlie its therapeutic actions have still not been identified but, in any case, this drug has now been withdrawn in the UK. 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

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