Tricyclic Antidepressant Drug, Chronic Pain and Overdose

Among TCAs, imipramine and clomipramine have been extensively studied. Both drugs are efficacious in the treatment of PD, and patients’ benefits concern the most important clinical aspects (panic attacks, anticipatory anxiety, and phobic avoidance behaviour). Clomipramine is suggested as being more efficacious than imipramine, indicating that drugs with predominantly serotoninergic effect may have greater antipanic effect. For this reason it is speculated that intravenous clomipramine could be a very effective agent in refractory cases because of the low desmethylation ratio (which maintains the 5-HT potency) compared with the same drug per os.

The side-effects of TCAs may be a major hindrance to their wider applicability in panic patients, being very sensitive to any symptoms imitating anxiety attack. An initial exacerbation of anxiety symptoms has frequently been noticed, and experts advise more gradual dose increases for panic patients than for depressed patients. The delay of onset of improvement is not an argument against the use of TCAs, considering the chronicity of PD.

Discontinuation symptoms have been described for antidepressants, but they have not been observed as a major problem in controlled studies, in contrast to treatment with alprazolam. The major advantages of antidepressants compared with BDZs are that physical dependence does not develop and that discontinuation can be instituted more rapidly. The optimal time to treatment discontinuation has not been determined. Patients are often initially treated for three months and responders continue treatment for 6–12 months, but some need longer maintenance treatment.

In a comprehensive review of the course and outcome of panic patients it was concluded that with modern treatment most patients will improve, but few will be cured. The presence of agoraphobia, depression and personality disorders indicates a poorer prognosis. Thus, a majority of patients may require long-term treatment. These issues were reviewed by Burrows et al. and they concluded that long-term treatment with TCAs did not lead to loss of efficacy, whereas high rates of relapse were observed after the discontinuation.

A systematic double-blind comparison of maintenance therapy for up to eight months in patients treated with alprazolam, imipramine or placebo showed that the therapeutic gains obtained in short-term trial persisted in all groups. Nevertheless, fewer placebo patients remained throughout the whole study period; TCAs were well tolerated and no intolerance to their efficacy was indicated. Another study of long-term treatment of PD showed that a higher percentage of patients withdrew from the placebo group than from the clomipramine and paroxetine groups.

A similar distribution of percentage was obtained with patients who withdrew owing to lack of efficacy. An unexpected finding was that the early observed, large placebo response persisted

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