Idiosyncratic intermittent nocturnal priapism occurring after quetiapine dose reduction

To the Editor

A 31-year-old male presented for workup of nocturnal painful erections occurring three to eight times at night. They were not provoked by anything and were relieved by walking and cold water. On further questioning, he reported a single episode of priapism that occurred 3 years ago upon starting treatment with 600 mg of quetiapine. His past medical history includes bipolar disorder. He specifically denied any personal or family history of blood disorders or sickle cell anemia. The patient denied tobacco use but reported once per month cocaine use. His symptoms started with quetiapine dose reduction from 300 to 25 mg. His current medications include alprazolam 0.5 mg daily, venlafaxine (75 mg), multivitamins and quetiapine 25 mg daily. The patient had a normal hemoglobin electrophoresis and a hypercoagulability workup was done that revealed a heterozygous C677T methylenetetrahydrofolate reductase (MTHFR) mutation and a heterozygous Factor V Leiden mutation. After ruling out any suspicion of an organic cause, the diagnosis of drug-induced priapism was made. Quetiapine was withdrawn. The frequency of the priapism episodes dropped acutely in the first week to once per night. After 1 month, the episodes had disappeared completely.

The onset of symptoms after a dose change in quetiapine and the regression of the symptoms after withdrawal of the medication make quetiapine the most probable cause behind this patient’s priapism. Cocaine has been frequently associated with priapism but is unlikely in this case given the temporal discrepancy. Antipsychotics are particularly renowned for causing priapism due to their alpha-1 adrenergic blockade. The association of second generation antipsychotics with priapism is still the subject of case reports. There are only 10 case reports of priapism occurring in the setting of quetiapine treatment. The doses reported were generally in the range of 300–700 mg, with one case taking 100 mg and one case taking 25 mg, but in conjunction with olanzapine and risperidone. We herein report the eleventh case of priapism occurring in the setting of quetiapine treatment. Among the other reported cases, we report the lowest dose.

To our best knowledge, this is the lowest reported dose of quetiapine associated with priapism. Our patient developed one episode of priapism upon starting quetiapine. He also developed recurrent episodes when the dose was lowered. This suggests that this particular side effect may be idiosyncratic instead of dose dependent. In addition, the cyclical and regular nature of the episodes suggests that they might be occurring during REM sleep. The mechanism of nocturnal penile tumescence is not completely understood. But one of the hypotheses is that testosterone-related excitatory neurons are allowed to manifest by inhibiting their inhibitory neurons in the locus coeruleus (Bancroft, 2005). Quetiapine may also have an effect on the regulation of this circuit.

One might be tempted to consider an association between the heterozygosity for Factor V Leiden and MTHFR on one hand and priapism. However, these two mutations are common in our population and most likely represent a coincidental finding.

What’s new?

• Lowest dose of quetiapine associated solely with priapism.

• Eleventh case report of priapism in the setting of quetiapine.

• Priapism is of an intermittent nocturnal fashion.

• Priapism occurred at dose reduction of quetiapine suggesting that this particular adverse event may be idiosyncratic.