Correspondence BIOL PSYCHIATRY 1i 77 1992;31:1172-1183 Rohrbaugh JW, Gaillard AWK (1983): Sensory and motor acetic acid levels in the cerebrospinal fluid of depressive aspects of contingent negativevariation. In Gaillard AWK, patients treated with pmbenecid. Nature 225:1259-1260. Ritter W (eds), Tutorials in ERP Research: Endogenous Van Praag HM, Kalm RS, Asnis GM, et al (1987): Den- Components. Amsterdam: Elsevier, pp 269-31 I. olosization of biological psychiatry or the specificity of Swerdlow NR, Koob GF (1987): Dopamine, schizophrenia, 5-HT disturbances in psychiatric discrders. J Affective mania and depression: Toward a unified hypothesis of Disord 13:1-8. cortico-striato-pallidothalamic function. Behav Brain Sci Walter WG, Cooper R, Aldridge VJ, McCallum WC, Win- 10:197-245. ter A (1964): Contingent negative variation: An electric Tyrer P, Owen RT, Cicchetti DV (1984): The brief scale sign of ~nsori-mot.or association of expectancy in the for anxiety: A subdivision of the comprehensive psy- humaii brain Nature 203:380-384. chopathological rating scale. J Neurol Neurosurg Psy- Widl6cher D (! 983): Psychomotorretardation: Clinical, the- chiatry 47:970-975. oretical and psychometric aspects. Psychiat Clin North Van Praag HM, Korf J, Puite J (1970): 5-Hydmxyindole- Am 6:27-40. Depression after Cyproheptadine: initial evaluation. Although no actual suicide attempts were reported, he described almost constant suicidal MAO Treatment ideation, which he resisted by increasing his physical To the Editor: activity until exhaustion. Cyproheptadine has been reported to be effec- During the year prior to evaluation, he had been tive in the treatment of anorgasmia induced by the attending weekly outpatient psychotherapy. Concom- administration of tricyclic antidepressants (Sovner itant with the psychotherapeutic intervention, several 1984; Steele and Howell 1986), monoamine oxi- medication trials had been attempted, including de- dase inhibitors (MAOIs) (DeCastro 1985), or sipramine, imipramine and nortriptyline, without re- fluoxetine (McCormick et al 1990). It has been lief of depressive symptoms. Trazodone was reported postulated that cyproheptadine's efficacy in treating of limited benefit, with a mild reduction in depressive this symptom is caused by the blockade of seroto- symptomatology, but severe sedation and orthostatic nin receptors. hypotension necessitated discontinuation of this agent. The administration of cyproheptadine for the treat- A trial of fluoxetine significantly reduced symptom- ment of antidepressant-induced sexual dysfunction atology after 6 weeks, but was also poorly tolerated has recently been associated with a recurrence of due to severe agitation and anxiety. depressive symptomatology in a series of three pa- In addition to a referral for cognitive-behavioral tients treated with fluoxetine (Feder 1991), as well therapy, phenelzine was initiated, to a maximum dose as with the reversal of therapeutic benefit in two pa- of 75 mg per day. After 5 weeks on this regimen, tients with bulimia nervosa, also treated with fluox- his depressive symptomatology remitted (HDRS score etine (Goldboom and Kennedy 1991). = 4). Suicidal ideation and self-injurious behavior, We report here a case of recurrence of depressive as well as the demanding, impulsive, and irritable symptoms after administration of cyptoheptadine in style noted in the initial presentation, were also mark- a patient who received full therapeutic benefit from edly diminished. tseatment with pheneizine. Concomitant with the resolution of his depressive Mr. C. is a 37-year-old man who presented for symptomatology, the patient reported difficulties in diagnosis and treatment of chronic depressive symp- sexual activity, with delayed ejaculation that later tomatology. Upon evaluation, he was severely de- progressed to anorgasmia. Treatment with cyprohep- pressed, with a blunted affect, as well as mood ir- tadine was initiated at a daily dose of 4 mg in an ritability, and a history of chronic impulsive self- attempt to reduce his sexual dysfunction. Within 3 injurious behavior, usually during the periods of more days of initiating this medication, nearly complete severe depression. A 17-item Hamilton Depression recurrence of depressive symptomatology was ob- Rating Scale (HDRS) score of 38 was obtained on served. No improvement of anorgasmia was reported 1178 BIOL PSYCHIATRY Correspondence 1992;31:1172-I 183 by the patient. Discontinuation of cyproheptadine Department of Psychiatry promptly reduced his depressive symptoms (HDRS University of Michigan Medical Center scores decreased from 22, 5 days after cessation of Ann Arbor, Michigan cyproheptadipe, to 6, 12 days after discontinuing treatment). At the present time, the patient reports a References moderate degree of delayed ejaculation, although he DeCastro DM (1985): Reversal of MAOI-induced anor- is no longer anorgasmic. gansmia with cyprohep~dine. Am JPsychiatry 142:783. We report here an instance of recurrence of de- Feder R (199I): Reversal of antidepressant activity of fluox- pressive symptomatology 3 days after the adminis- etine by cyproheptadine in three patients. J Clin Psy- tration of cyproheptadine in a patient who had re- chiatry 52:163-164. sponded fully to treatment with the MAOI phenelzine. Goldboom DS, Kennedy SH (1991): Adverse interaction of This phenomenon has been reported previously, in a fluoxetine and cyproheptadine in two patients with bu- similarly rapid time course (few hours to 4 days), in limia nervosa. J Clin Psychiatry 52:261-262. three patients responsive to the serotonin-reuptake McCormick S, Olin J, Brotman AW (1990): Reversal of blocker, fluoxetine (Feder 1991). Cyproheptadine may fluoxetine-induced anorgasmiaby cypmheptadine in two lead to a revetsal of clinical benefit when adminis- patients. J Clin Psychiatry 51:383-384. tered for the treatment of antidepressant-induced an- Sovner R (1984): Treatment of tricyclic antidepressant-in- orgasmia. Close observation of patients treated with duced orgasmic inhibition with cyproheptadine. J Clin Psychopharmacol 4:169. this regimen is suggested. Steele TE, Howell EF (1986): Cyproheptadine for imipra- mine-induced anorgasnda. J Clin Psychopharmacol John Kar Zubieta 6:326--327. Mark A. Demitrack Sodium Valproate Augmentation weight loss, sleep disturbance, and feelings of guilt. of Fluoxedne or Fluvoxamine Effects The general practitioner treated the woman with imipramine, which caused a rash, and benzodiaze- To the Fditor: pines. Treatment with clomipramine, then with t:ontaine et al (1991) described the addition of lith- clomipramine and tryptophan, was not completely ium to fluoxetine in the treatment of refractory depres- effective and she was unable to stop the diazepam sion. This is likely to be a major advance if lithium because of continuing feelings of anxiety. There was augments the action of fluoxetine without producing a also a severe tremor so these drugs were gradually potf~ntially dangerous hyperserotonin syndrome (CSM withdrawn. A course of electrconvulsive therapy 1919). For cases in whom there are contraindications (ECT) helped temporarily but was followed by a to the use of lithium carbonate, the introduction of so- rapid deterioration. Eighteen months after initial re- dium valproate may be considered. The use of sodium ferral, fluoxetine was started and was increased valproate in the treat~ient of affective illness has been gradually to 20 mg TID, and nifedipine, which might previously described (Emrich et al 1985), but it also have been maintaining the depression, was discon- appears to have an augmenting effect on the specific tinued. The patient was discharged on fluoxetine 60 serotonin reuptake inhibitors fluoxetine and fluvox- mg mane only, but 3 weeks later reported severe amine. Two cases are described in some detail. depression, wakening with panic at 5:00 A.M., diur- nal variation of mood, and poor appetite. Fluoxe- Case 1 tine was reduced to 20 mg mane, sodium valproate was added, and 4 weeks later there was a marked A ~7-year-old woman was referred with a 2- improvement. Six weeks after the introduction of month history of panic attacks and depression with valproate the patient was completely free fr~,m pan- .