neuroleptic treatment or reducing medication levels. It differs from the classical withdrawal symptoms, first, by the absence of cholinergic symptoms but, above all, by prompter relapse after cessation of treatment and more sudden, and sometimes more intense, recurrence of symptoms, often with the appearance of new symptoms not previously reported in the patient’s history (2). The clinical description of this concept is reflected in the 3 case reports described above. A functional dopaminergic rebound at the mesolimbic level may be responsible for the clinically observed psychotic rebound.

On sudden withdrawal, both olanzapine and clozapine can produce signs of supersensitivity psychosis (3). Antipsychotic treatment must thus be maintained at a constant dose. In severe forms of the disorder, it may be advisable to prescribe an associated anticonvulsant treatment (phenytoin, carba- mazepine, or valproic acid).

We consider that introducing the concept of supersensitivity into the broad field of resistance to neuroleptics may allow differentiated, specific-care protocols to be designed.

References

1. Chouinard G, Annable L, Ross-Chouinard A, Holobow N. A ten-year follow-up study of supersensitivity psychosis. Biol Psychiatry 1990;27:140 A.
2. Chouinard G, Jones BD. Neuroleptic induced supersensitivity psychosis: clinical and pharmacological characteristics. Am J Psychiatry 1980;137:16–21.
3. Llorca P-M, Penault F, Lancon C, Dufumier E, Vaiva G. Notion de psychose d’hypersensibilite. Cas particulier de la clozapine. L’Encéphale 1999 ; XXV : 638–44.

Pierre-Michel Llorca, MD
Clermont-Ferrand, France
Guillaume Vaiva, MD, PhD
Lille, France
Christophe Lancon, MD, PhD
Marseilles, France

Dear Editor

Galactorrhea is an uncommon side effect of many psychoactive medications.

Antipsychotics may cause galactorrhea by blocking the dopaminergic inhibition of prolactin release from the anterior pituitary. There are rare reports of galactorrhea with the tricyclic antidepressants (1,2) as well as with the selective serotonin reuptake inhibitors (SSRIs) (3–7). The observed lactation is presumed to be secondary to a drug-mediated increase in prolactin secretion, although prolactin levels are often not documented in these case reports. We report a case of hyperprolactinemia and galactorrhea following treatment with paroxetine.

In mid-November 1999, a 32-year-old woman was started on paroxetine 20 mg daily to treat her first episode of major depression. Because of partial response to the medication, the dose was increased to 40 mg daily in early December. By early January 2000, she reported feeling euthymic. At the end of January, trazodone 25 mg as required was prescribed for intermittent insomnia. Her only other medication was Tylenol #3, 1 tablet daily, for chronic pain secondary to sacroileitis.

In mid-February, she became alarmed when she began to lactate spontaneously. She consulted her gynecologist, who recommended neuroimaging to rule out a pituitary adenoma. A physical exam, CT scan, and magnetic resonance imaging (MRI) were all normal. Serum prolactin level on March 24, 2000, was 46.1 mcg/L (normal is 20 mcg/L).

Paroxetine was discontinued on March 31, and on April 3 the patient’s serum prolactin was 7.4 mcg/L.

Unfortunately, in mid-April she had an abrupt switch to mania with elevated mood, decreased sleep, racing thoughts, and grandiosity. She was admitted with a diagnosis of bipolar disorder, type I, manic episode, and received 1 week of quetiapine 50 mg daily in addition to lithium 600 mg daily. During this admission, serum prolactin levels remained in the normal range (11 mcg/L on April 27; 18 mcg/L on April 28), and spontaneous

lactation stopped, but breast milk could still be expressed with palpation. It was noted that her thyroid was enlarged. An endocrinologist was consulted, and Hashimoto’s thyroiditis was diagnosed, based on a high antithyroperoxidase titre of 1739 (normal 35 IU/ml) and a transiently elevated thyroid-stimulating hormone (TSH) of 5.69 (normal 0.3 to 5.5 MIU/L). Previous and subsequent TSH measurements have all been in the normal range. The endocrinologist felt that the briefly elevated TSH had not significantly contributed to the prolactin elevation. His diagnostic impression was that paroxetine was the primary cause of the prolactin elevation and the resulting galactorrhea. At no time did the patient experience amenorrhea; however, during this period her menstruation lasted an unusually long 7 to 10 days.

This case demonstrates the development of hyperprolactinemia while receiving paroxetine that subsided shortly after the discontinuation of the medication. The delay between cessation of the drug and cessation of galactorrhea was somewhat longer than the 3 to 4 weeks previously reported with SSRIs (6,7); it may have occurred because of antipsychotic medications that the patient received during her acute manic phase (which occurred 4 weeks after discontinuation of paroxetine).

The mechanism by which serotonergic agents produce hyperprolactinemia is not clear. There is evidence that serotonin may stimulate prolactin release directly via postsynaptic 5-HT receptors in the hypothalamus (8), or indirectly by 5-HT–mediated inhibition of tubuloinfundibular dopaminergic neurons (9). Clearly, the interactions between the dopaminergic and serotonergic systems throughout the brain are complex, because SSRIs occasionally cause side effects normally associated with antipsychotic medications, such as extrapyramidal symptoms (9) and neuroleptic malignant syndrome (10). It is interesting to note in this case that lactation started shortly after trazodone, a 5-HT₂ antagonist and weak SRI, was added. Whether it is coincidence or