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Figure 1. The 5-HT-1 serotonin receptor is associated with the antidepressant effect and reduced anxiety levels, while the 5-HT-2 receptor is a mediator of increased anxiety levels, insomnia and sexual dysfunction. The 5-HT-2 receptor is hypersensitive in patients with anxiety disorders (which is symbolized in the figure by the greater size of this receptor). 5-HT: 5-hydroxytryptamine.
(Figure omitted. See article PDF.)
Figure 2. Inhibition of the presynaptic reuptake of serotonin leads to the downregulation of postsynaptic receptors (symbolized in the figure by the reduction in the receptor size), therefore improving the effects of 'hyperfunction' of the receptor 5-HT-2c. 5-HT: 5-hydroxytryptamine.
(Figure omitted. See article PDF.)
Panic disorder (PD) is a lifelong, chronic and recurring condition, and affects 1.6-2.2% of the global population [1]. The pharmacological treatment of PD, over recent years, has included antidepressants and benzodiazepines [2]. Among the antidepressants, initially there were the monoamine oxidase inhibitors and the tricyclic antidepressants [2].
The tricyclic antidepressants, especially imipramine [3-5] and clomipramine, were widely tested for PD [6]. Desipramine was also considered efficient [7]; however, fewer studies were available for this drug compared with imipramine. Nortriptyline was less systematically studied for use in PD [8], but clinical experience indicates that it is also efficient and perhaps better tolerated than other tricyclic antidepressants [9].
In spite of proven efficacy, tricyclic antidepressants have an unfavorable side effect profile, which, very often, leads to the discontinuation of the treatment [10]. This class of drugs has presented a high degree of cardiotoxicity, with increased risk of sudden death and high lethal potential in the case of overdose [9,10].
The selective serotonin-reuptake inhibitors (SSRIs) class of antidepressants were developed in an effort to produce drugs that had the same effect as the tricyclic antidepressants, but in a more selective manner, therefore producing fewer problematic side effects and an increasing safety profile. The SSRIs do not present four of the pharmacological properties that characterize the tricyclics: the blockage of muscarinic, H1-histaminergic and α1-adrenergic receptors and adrenergic and norepinephrine reuptake inhibition, leaving the property of serotonin reuptake inhibition as the principal characteristic [9].
As a result, in the last decades, the SSRIs have emerged as the first-line treatment for PD [11-13].
The objective of this article is to undertake an up-to-date, systematic review...