Panic disorder is a chronic condition for many patients and can be socially, emotionally and occupationally disabling. Until recently, clomipramine and alprazolam were the only drugs approved for its treatment. While widely used in the US and Europe, both belong to drug classes (tricyclics and benzodiazepines) with well-recognised side effects that can be problematic and thus limit their use. Recently, paroxetine became the first selective serotonin reuptake inhibitor to receive approval and licensing for panic disorder.

The short- and long-term efficacy and tolerability of paroxetine in panic disorder has been established in clinical trials of almost 1,000 patients meeting Diagnostic and Statistical Manual (DSM)-IIIR criteria for panic disorder, with or without agoraphobia. In a 12-week double-blind study of 120 panic patients receiving standardised cognitive therapy, paroxetine was significantly more effective than placebo in reducing panic attack frequency. In a 12-week placebo-controlled comparison in 367 panic patients, paroxetine was at least as effective as clomipramine and better tolerated. There was also some evidence that paroxetine had an earlier onset of action than clomipramine.

A 9-month extension of the placebo-controlled comparison with clomipramine showed that the efficacy of paroxetine and clomipramine is maintained when treatment is continued into the longer term. In a relapse prevention study, 105 responders to 3 months' treatment with paroxetine or placebo were re-randomised, either to continue existing treatment or to receive placebo for 3 months. Only 5% of patients who continued to take paroxetine experienced a relapse compared with 30% of those who switched to placebo (P = 0.002). Paroxetine was generally well tolerated. In the short-term trials, the frequency of withdrawals due to adverse events (7.3%) was lower than that for placebo (11.4%) or clomipramine (14.9%). In the longer term, the dropout rate due to adverse events increased in the clomipramine group (19.0%) but was unchanged in the paroxetine group (7.4%). Since most patients with panic disorder will require prolonged treatment, the long-term tolerability of paroxetine and its lack of potential for dependence are important advantages that will encourage good compliance with treatment and improve the quality of life of patients.

Panic disorder is widespread in Australia, often in combination with other psychiatric conditions such as agoraphobia or major depression. Pharmacotherapy for panic disorder in Australia commenced with benzodiazepines, and later progressed to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). More recently, treatment has moved towards use of the selective serotonin reuptake inhibitors (SSRIs), which are effective and better tolerated. Paroxetine is the first drug of this class to receive approval for treatment of panic disorder in Australia.

A clinical and biological pattern similar to that of neuroleptic malignant syndrome is reported in a depressed patient treated with trimipramine, without any concomitant use of neuroleptics. The antidopaminergic properties of this drug, one of the tricyclic antidepressants, may account for this uncommon side effect.

The writers of this paper made an inventory of the studies on the use of thyroid hormone in the treatment of depression. Fifteen clinical trials (353 patients), published between 1969 and 1987. were found, that can be described, as to their design, in two seperate groups:

One group (7 studies) administers thyroid hormone simultaneously with a tricyclic antidepressant to reach a faster effect of the antidepressant. The other group (8 studies) adds thyroid hormone to a tricyclic antidepressant in patients who fail to respond to this treatment, with the aim to convert therapeutic failure to success. After studying the literature we think we are able to conclude that it can be usefull to combine the antidepressant with thyroid hormone in view of the fact that, in a number of depressed patients, it shortens the duration of the illness. The augmentation of tricyclics by thyroid hormone needs further study.

Objectives: Literature reports on SSRI associated discontinuation symptoms are variable. As a result, the prevalence of an antidepressant halo effect can not be ruled out. This survey aims to assess the awareness and experience of these symptoms among doctors in Ireland.

Method: Questionnaires were sent to a random sample of 100 GPs, NCHDs and consultants. A questionnaire measured awareness, experience and reported severity, of SSRI discontinuation symptoms as opposed to TCAs, the latter being used as ‘controls’. Data was statistically analysed using SPSS (Windows Version 8.0).

Results: Response to the questionnaire was as follows: 37% of GPs (n = 37), 35% consultants (n = 35) and 18% NCHDs (n = 18). Comparisons were made between the three groups. There was significant variability in the reported recognition and severity of symptoms specific to the SSRI discontinuation syndrome within and between the groups. Overall NCHDs attribute less discontinuation symptoms to SSRIs (p = 0.038) and GPs attribute more to TCAs (p = 0.03).

Conclusions: Doctors tend to generalise discontinuation symptoms to all antidepressants with significant variation in reporting practices. Thus there is a need for randomised control studies to aid the recognition and prevention of the discontinuation syndrome.

Therapeutic drug monitoring of tricyclic antidepressants is a controversial issue. A case is reported in which a patient with recurrent depression developed asymptomatic tricyclic toxicity while on trimipramine, a tricyclic antidepressant, and diltiazem, a calcium channel blocker. A metabolic interaction involving cytochrome P450 3A (CYP3A) is postulated. It is suggested that routine therapeutic drug monitoring of tricyclic levels should be an essential part of the management of depression.