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Home , Cyproheptadine, Imipramine, Tricyclic, Tricyclic antidepressant

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 or the specificity of Swerdlow NR, Koob GF (1987): , , 5-HT disturbances in psychiatric discrders. J Affective mania and : 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 : 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 : initial evaluation. Although no actual 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 induced by the attending weekly outpatient psychotherapy. Concom- administration of (Sovner itant with the psychotherapeutic intervention, several 1984; Steele and Howell 1986), monoamine oxi- trials had been attempted, including de- dase inhibitors (MAOIs) (DeCastro 1985), or sipramine, and , without re- (McCormick et al 1990). It has been lief of depressive symptoms. was reported postulated that cyproheptadine's 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. necessitated discontinuation of this agent. The administration of cyproheptadine for the treat- A trial of fluoxetine significantly reduced symptom- ment of -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 , 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 , also treated with fluox- his depressive symptomatology remitted (HDRS score etine (Goldboom and Kennedy 1991). = 4). 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 - 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 -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 Augmentation weight loss, sleep disturbance, and feelings of guilt. of Fluoxedne or Effects The general practitioner treated the woman with imipramine, which caused a rash, and benzodiaze- To the Fditor: pines. Treatment with , then with t:ontaine et al (1991) described the addition of lith- clomipramine and , was not completely ium to fluoxetine in the treatment of refractory depres- effective and she was unable to stop the sion. This is likely to be a major advance if 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 , 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 , 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 . Two cases are described in some detail. depression, wakening with panic at 5:00 A.M., diur- nal variation of mood, and poor . 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-