MORE ON FLUVOXAMINE AND ENURESIS

To the Editor:

Mesaros (1993), while treating a patient for dysthymia, dis-covered the therapeutic effect of selective serotonin reuptakeinhibitors (SSRIs) on nocturnal enuresis. MacLean (1960),while treating emotional problems in a patient, noticed thatimipramine, one of the tricyclic antidepressants, improved thepatient’s enuresis. We also have reported that fluvoxamine, oneof the SSRIs, was effective for two children with obsessive-compulsive spectrum disorders and nocturnal enuresis and thatSSRIs may become a new drug for the treatment of nocturnalenuresis according to the results in our two patients, a smallcase series (Kano and Arisaka, 2000), and other reports on thevalidity of SSRIs for nocturnal enuresis. We wish to reply tothe comment on our letter by Horrigan and Barnhill (2000).

The effect of fluvoxamine was investigated in 18 children(7 girls, 11 boys) aged between 7 and 13 years (mean ± SD, 9.1 ±1.7 years) with a diagnosis of monosymptomatic nocturnalenuresis and no psychiatric diseases. All patients were treatedwith motivation therapy, conditional therapy, and bladderretention + training before pharmacological therapy, but thesewere not effective. Twelve of the 18 patients were given imipra-mine at a dose of 1 mg/kg orally at bedtime for 2 months. In 4(33%) of these 12 patients, the frequency of nocturnal enuresisdecreased. These results are similar to those previously reportedin the literature (32%). We also administered desmopressin in11 of 18 patients at a dose of 10 to 20 μg intranasally at bed-time for 3 months. In 8 (73%) of these 11 patients, the fre-quency of nocturnal enuresis decreased.

We initially administered fluvoxamine at a dose of 25 mg atbedtime 1 month after the cessation of imipramine or desmo-pressin. If the patient remained incontinent after 2 months, weincreased the dosage to 50 mg (8 of 18 patients). Informed con-sent was obtained from both the children and their parents. Weobtained laboratory values (serum total protein, total cholesterol,creatine kinase, renal and hepatic function tests, and electrolytes)with an automated analyzer (Hitachi 7450, Tokyo, Japan) beforeand every 2 months after the initiation of fluvoxamine treatment.We also measured the peripheral complete blood cell count.

Fluvoxamine was completely effective in 5 of 18 patients,and to date these 5 patients have had no recurrence of nocturnalenuresis after the cessation of fluvoxamine. The frequency ofnocturnal enuresis decreased in nine patients treated with flu-voxamine, and these nine patients have been treated for 4 to 13months. One patient for whom fluvoxamine was not effective

also did not respond to other drugs. Three of four patients forwhom fluvoxamine was not effective responded to desmopres-sin. Conversely, two of seven patients for whom fluvoxaminewas effective did not respond to desmopressin. Two patients hadheadache and one had nausea, but these adverse effects dis-appeared with continued fluvoxamine treatment. No seriousclinical adverse effects or abnormal laboratory data were noted.

Fluvoxamine was effective in 14 (78%) of 18 patients, whoconsisted of 5 (83%) of 6 patients with secondary nocturnalenuresis and 9 (75%) of 12 patients with primary nocturnalenuresis. The effectiveness rate of fluvoxamine was similar tothat of desmopressin. Water intoxication associated withexcessive water intake before bedtime is an uncommon butserious adverse effect of desmopressin, and patients with waterintoxication present with a seizure, changes in mental status, orboth (Apakama and Bleetman, 1999). Imipramine has impor-tant adverse effects, and overdoses can be lethal. Fluvoxaminehad no serious adverse effects in our small case study. Inasmuchas children with nocturnal enuresis have a favorable long-termprognosis, it is important to consider the serious adverse effectsof drugs. The exact mechanism by which SSRIs could be ben-eficial in the treatment of nocturnal enuresis remains to beelucidated, but SSRIs (such as fluvoxamine) may be clinicallyuseful for the treatment of nocturnal enuresis because they haveno serious adverse effects and higher validity than imipramine.Time will tell whether the validity of SSRIs for nocturnalenuresis will withstand scrutiny for our suggested application.

Kenichi Kano, M.D.Osamu Arisaka, M.D.

Dokkyo University School of Medicine, Japan

Apakama DC, Bleetman A (1999), Hyponatraemic convulsion secondary to des-mopressin treatment for primary enuresis. J Accid Emerg Med 16:229–230

Horrigan JP, Barnhill LJ (2000), Fluvoxamine and enuresis (comment onletter). J Am Acad Child Adolesc Psychiatry 39:1465–1466

Kano K, Arisaka O (2000), Fluvoxamine and enuresis (letter). J Am AcadChild Adolesc Psychiatry 39:1464–1465

MacLean REG (1960), Imipramine hydrochloride and enuresis (letter). Am JPsychiatry 117:551

Mesaros JD (1993), Fluoxetine for primary enuresis (letter). J Am Acad ChildAdolesc Psychiatry 32:877–878

HALOPERIDOL DECANOATE IN CHILDREN

To the Editor:

The use of neuroleptics in children and adolescents withnonpsychotic disorders is not uncommon. In addition to their

L E T T E R S T O T H E E D I T O R

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