Cns Drugs
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Paroxetine is the first selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) to be approved for the treatment of patients with panic disorder with or without agoraphobia. It is a highly selective inhibitor of presynaptic serotonin reuptake and does not interact with adrenergic, dopaminergic, histaminergic or serotonergic receptors to any significant extent. Oral paroxetine 10 to 60 mg/day is significantly more effective than placebo in reducing the frequency of panic attacks and improving associated symptoms, as shown in short term trials in patients with panic disorder with or without agoraphobia. The efficacy of the drug was maintained during up to 6 months'; treatment, and continued therapy reduced the risk of relapse. Oral paroxetine 10 to 60 mg/day was at least as effective as clomipramine 10 to 150 mg/day, but appeared to have a more rapid onset of effect, in a placebo-controlled trial. The tolerability profile of paroxetine is similar to that established for other SSRIs and is characterised by adverse events such as nausea, headache, somnolence, dry mouth, tremor, insomnia, asthenia, sweating, constipation, dizziness and sexual dysfunction. Paroxetine was better tolerated overall than clomipramine and was associated with a lower incidence of certain anticholinergic events (such as dry mouth and constipation) in a comparative trial. It is not associated with the type of dependence seen with benzodiazepines, and it appears to be safer in overdose than the tricyclic antidepressants. Paroxetine 20 or 30mg does not significantly impair psychomotor function or interact with alcohol (ethanol). In conclusion, the good tolerability profile of paroxetine, including lack of dependence potential and relative safety in overdose, makes it attractive for the treatment of patients with panic disorder. It appears to be at least as effective as clomipramine in reducing panic attacks and associated symptoms. Although further trials to compare the efficacy and tolerability of paroxetine with that of other tricyclic agents (especially Imipramine), high-potency benzodiazepines and monoamine oxidase inhibitors are needed, the drug appears to have the potential to become a first-line treatment for panic disorder. ⋯ Paroxetine is generally well tolerated by both younger and older individuals and its adverse event profile is consistent with that expected for an SSRI. The tolerability profile of paroxetine in patients with panic disorder appears to resemble that in patients with depression. Headache, nausea, somnolence, dry mouth and insomnia were the most common adverse events among 469 patients with panic disorder who received paroxetine 10 to 60 mg/day in short term clinical trials. The individual incidences for these events ranged from 18 to 25%; however, the incidence of headache in paroxetine-treated patients was the same as that in placebo recipients. (ABSTRACT TRUNCATED)
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Mirtazapine is a tetracyclic antidepressant with a novel mechanism of action; it increases noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors. The increased release of serotonin (5-hydroxytryptamine; 5-HT) stimulates serotonin 5-HT1 receptors because mirtazapine directly blocks 5-HT2 and 5-HT3 receptors. The enhancement of both noradrenergic- and 5-HT1 receptor-mediated neurotransmission is thought to be responsible for the antidepressant activity of mirtazapine. In short term (5 to 6 weeks) clinical trials in patients with depression. mirtazapine produces clinical improvements significantly superior to those of placebo, similar to those of tricyclic antidepressants (TCAs) [amitriptyline, clomipramine and doxepin] and possibly superior to those of trazodone. Short term clinical tolerability data suggest that mirtazapine produces fewer anticholinergic-, adrenergic- and serotonergic-related adverse events than TCAs. In rare cases, mirtazapine, in common with many antidepressants, was associated with potentially serious changes in haematological parameters (e.g. agranulocytosis and neutropenia). The drug appears to be safe in overdose and possesses a very low propensity for inducing seizures. Comparisons with other classes of antidepressants are needed to determine the relative position of mirtazapine in clinical practice. However, preliminary data indicate that mirtazapine, with its novel mechanism of action, is a promising addition to currently available options for the treatment of depression. ⋯ The recommended starting dosage of mirtazapine is 15 mg/day for 4 days, then 30 mg/day for 10 days. If effective, the drug should be continued unchanged at this dosage or, in patients assessed as insufficiently improved, the daily dosage may be further increased to 45 mg/day. In patients with hepatic or renal insufficiency, careful dosage titration as well as regular and close monitoring for adverse events is recommended. Concomitant use of mirtazapine and diazepam or alcohol (ethanol) may also impair cognitive and/or motor performance.