Letters to the Editor

Nord J. Psychiatry, 52/5 1998. p. 440-441

Dex-chlorpheniramine treatment of panic disorder

In current clinical practice, panic disorder and agoraphobia are commonly and successfully treated with selective serotonin reuptake inhibitors (SSRIs) (1). Serotonin reuptake inhibition, as a drug mechanism, was discovered in the late 1960s, and in 1969 Arvid Carlsson reported this effect in miscellaneous drugs, including the antihistamine chlorpheniramine (2, 3). This was the starting point for the development of zimeldine, the first SSRI, effective in both panic disorder and depression (4). The molecular structure of zimeldine is strikingly similar to that of the pheniramines (5). To our knowledge, no trials of pheniramines in psychiatric disorders have been presented.

By serendipity, we observed a patient whose agoraphobia and panic attacks seemed to respond to dex-chlorpheniramine.

Case report

A 38-year-old woman had had two periods of agoraphobia with panic attacks. The first period was connected with a complicated divorce process. Later on she met her present husband, and it was believed that this stable relationship contributed to the cessation of her anxiety symptoms. Then she became pregnant, and the recurrence of her anxiety attacks and phobias was unexpected. During the pregnancy and breast-feeding she became totally housebound, unable even to cross the front garden. Treatment with clomipramine was started and resulted in some amelioration at a dose of 25 mg/day. The patient was reluctant to increase the dosage due to orthostatic hypotension. At this point, however, it was brought to light that the patient had been taking systemic antihistamines against hay fever continuously for several years before her pregnancy. During the first agoraphobic period she had used clemastine, a non-pheniramine antihistamine with negligible serotonin reuptake inhibition. Shortly after her second marriage this was changed to dex-chlorpheniramine. This medication was continued during the healthy period until she became pregnant. When her medication was withdrawn out of concern for the foetus, phobias and panic attacks returned. Associating this history with the above biochemical findings. we added dex-chlorpheniramine, 12 mg/ day. instead of increasing her clomipramine. The result was a complete cessation of attacks.

We have tried dex-chlorpheniramine in nine other patients with panic disorder. Six of these have responded favourably, sometimes dramatically so. A dosage of 12 to 24 mg/day was used. Except for the occurrence of sedation in some patients (expected with an antihistamine), side-effects were similar to but milder than those of SSRIs. One patient developed nausea. and two had increased sweating. Most side-effects subsided with continued treatment.

These cases warrant controlled studies to confirm the efficacy in panic disorder of pheniramines, drugs that have been used for decades as antihistamines with no known long-term side-effects. Public funding will probably be needed. since no company will be willing to test old drugs without patent protection. In fact, the manufacturer of the pheniramines was informed about Carlsson's discoveries in the early 1970s but was not interested in new psychiatric indications for their antihistamines.

References

  1. Sheehan DV, Harnett-Sheehan K. The role of SSRls in panic disorder. J Clin. Psychiatry 1996:57 Suppl 10:51-8.

  2. Carlsson A, Lindqvist M. Central and peripheral monoaminergic membrane-pump blockade by some addictive analgesics and antihistamines. J Pharm Pharmacol 1969;21:460-4. 

  3. Meek JL, Fuxe K, Carlsson A. Blockade of p-chloromethamphetamine induced 5-hydroxytryptamine depletion by chlorimipramine, chlorpheniramine and meperidine. Biochem Pharmacol 1971;20:707-9.

  4. Carlsson A, Wong DT. Correction: a note on the discovery of selective serotonin reuptake inhibitors. Life Sci 1997;61:1203.

  5. Agurell S. The research and development of a 5-HT selective reuptake blocker. Preclinical aspects. Acta Psychiatr Scand 1983;68 Suppl 308:19-24.

Mats Humble, M.D., and Einar Hellbom, B.A., Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Division of Psychiatry, Huddinge University Hospital, M59,SE-141 86 Huddinge, Sweden.