Antihistamines, selective serotonin reuptake inhibitors, and panic disorder

Nord J. Psychiatry, 53/2  1999, p. 100

E. HELLBOM, M. HUMBLE. M. LARSSON

The development of' the selective serotonin reuptake inhibitors (SSRIs) was to it large extent based on research by Professor Arvid Carlsson and colleagues. The first SSRI, zimelidine, is closely related to the pheniramines, a group of antihistamines with documented serotonin reuptake inhibition. To verify clinically the original findings of' Carlsson. a small open study was performed with the antihistamine dex-chlorpheniramine (dCP) in panic disorder, an SSRI-responsive condition.

Ten patients with panic disorder who were reluctant to take available antidepressants, were treated with dCP. 12-24 mg/day. The result of tile treatment was evaluated by means of Clinical Global Impression-Change (CGI-C). In one patient serotonin in whole blood (WB-5HT) was measured at base line and after 8 weeks of treatment.

After 8 weeks of treatment 7 of the 10 patients had no or few panic episodes. In four of five patients with concomitant agoraphobia, the phobic avoidance had decreased significantly. The most common side-effect was initial but transient sedation, typical of' the classical antihistamines. Some patients reported side-effects similar to, but milder than, those of the SSRls: nausea in one case and increased sweating in two cases. Most side-effects subsided with continued treatment. As expected during a serotonin reuptake-inhibiting treatment, WB-5HT decreased from 81 to 37 mg/l.

dCP, an antihistamine widely used since the sixties, with few and mild side-effects, was found clinically effective in an uncontrolled study of patients with panic disorder. The clinical results are corroborated by the biochemical findings. Accordingly, we have also found that some patients who originally had anxiety disorders may experience significant relapses when switched from long-term pheniramine treatment to other antihistamines not inhibiting serotonin reuptake. As predicted by Carlsson, antihistamines with strong sertonin reuptake properties like chlor- or brom-pheniramines may be clinically useful in conditions otherwise treated with SSRls, such as anxiety disorders. Controlled studies to further evaluate these findings are warranted.