CASE REPORT

JAVAD H. KASHANI, M.D.

KAY K. HODGES, Ph.D.

WAllO O. SHEKIM, M.D.

Hypomanic reaction toamitriptyline in a depressed childTricyclic antidepressants enjoy widespread use by psy­chiatrists and pediatricians for a variety of disorders inchildren, inclutling enuresis, school phobia, hyperkine­sis and depression. I Currently, the most widely em­ployed are imipramine and amitriptyline. A review ofthe literature reveals that a variety ofinvestigators haveused amitriptyline in children; some of the reports haveincluded side-effects. For instance, Frommer2 usedamitriptyline (up to 100 mgl24· hours) in children;side-effects included sleepiness, nausea, constipation,and hysterical behavior. Lucas and associates3 in adouble-blind study using amitriptyline (30 and 50 mglday in younger and older children, respectively), re­ported marked drowsiness in one of the older patientsafter each 50-mg dose. However, on dosage reductionto 30 mg/day, the side-effect promptly disappeared.Although hypomanic reactions to tricyclic antidepres­sants have been reported in the adult literature,4 to ourknowledge there have been no similar episodes re­ported in depressed children treated with amitriptyline.

c•• reportAn obese (72 kg) 11-year-old boy was referred to the childpsychiatry inpatient service because of refusal to attendschool, reading disability, feeling frightened, and difficulty inconcentrating and getting along with others. Sadness,

Drs. Kashani and Hodges are assistant professors ofpsychiatryand Dr. Shekim is associate prOfessor ofpsychiatry, Section ofChild Psychiatry, University ofMissouri, School of Medicine.Reprint requests to Dr. Kashani, 803 Stadium Road, Columbia,M06520J.

OCTOBERI~'VOL21'NOIO

hopelessness, and apprehension were prominent features.He had insomnia, cried easily, complained of being tired,and blamed himself for his parents' divorce. He thought itwould be easier to die than to live, and was generallypreoccupied with death and killing. He had been diagnosedas hyperactive at age 5, and was noted to be overactive onadmission. His appetite was insatiable. During the firstevening following admission, after completing his own din­ner he stole and consumed the entire dinner of one of thestaff. His family background incluaed an alcoholic fatherand a mother who had a history of bipolar depression.

At the time of his admission, the authors were engaged inan ongoing research project comparing the effects.of ami­triptyline with placebo. This patient fit the Research Diag­nostic Criteria for major depressive disorder; therefore, themother was informed of the study, and both she and her songave signed consent according to the requirements of theCommittee for Research Involving Human Subjects of theUniversity of Missouri Medical Center. The research proto­col was a double-blind, cross-over design in which eachchild was evaluated at baseline, after four weeks of treat­ment with amitriptyline, and after four weeks of receivingplacebo. The children were randomly assigned to the pla­cebo-amitriptyline condition or the amitriptyline-placebocondition. The Medical Center pharmacist makes theseassignments for order of treatment. None of the ward staff,inclUding the child psychiatrist, nor the patient and hisfamily were aware of the identity of the "medication" beingadministered. The "medication" began with an initial dos­age of 1 mg/kg/day and was scheduled to be increasedafter three days to 1.5 mg/J<g/day.

No significant behavioral differences were noted by wardnurses during the first four-week observation period eitherbefore or after institution of the "medication." However, the

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Case report

patient reportedly became more accustomed to ward rou­tine and felt more comfortable during this interval.

After switching of the patient to the second "medication,"a change was noted. On the seventh day of administration,and while the patient was at home on leave of absence, hismother called and stated that her son had been sleepingexcessively, and tlad dilated pupils. The "medication" wasstopped for about 36 hours, aUer which the boy's symptomspromptly disappeared. However, because of the potentialunreliability of the mother's report, the "medication" wasreinstituted.

On the si~h day of reinstitution, it was reported by theoccupationai therapy, nursing, recreational therapy, andeducation staff that the child was exhibiting excessiveirritability and anger, pacing excessively and declaring thathe was not afraid anymore, that he was "not a chickenanymore." He became openly defiant, belligerent, hostile,and argumentative, speaking constantly in a loud voice,with pressure of speech.

The following day the boy became hoarse (secondary toconstant loud talking) and was impossible to manage in theward. Although the ward child psychiatrist was still blind tothe identity of the medication being administered, the clini­cal indications suggested that this second medication couldhave been amitriptyline. The psychiatrist reduced the dos­age to the initial level of 1 mg/kg (70mg/day) for theremainder of the four-week study. This decision was notdiscussed with other ward staff. Within 48 hours, the hypo­manic reaction disappeared, but the child's behavior con­tinued to improve dramatically: he was no longer withdrawn,did not cry easily, and felt stronger and happier. Improve­ment was rioted in most of his depressive symptomatology,including mood, activity level, and ability to concentrate(which was surprising to his teachers). In addition, he nolonger exhibited suicidal thoughts, became more involvedwith ward activities and other children, and improved mark­edly in his learning.

Discussion

This child's hypomanic reaction could conceivablyhave been due to a placebo effect; however, it has beenshown that drowsiness and gastrointestinal complaints,rather than hypomania, are the more common reac­tions to placebo.s In addition, the study was blind and itwas only at the study's conclusion, when the code wasbroken, that the patient's reaction could be attributedto amitriptyline. It is conceivable that this reaction mayhave represented the initial episode. albeit at a young

age, in the spontaneous development of hypomania.However, onset of the hypomania with increasing dos­age, coupled with its disappearance on tapering of thedosage, strongly implicate amitriptyline as the etiologicagent.

Since a similar reaction was not observed in threeother boys receiving the same medication (and athigher dosages), a predisposition to manic reactionwould seem to be the most logical conclusion. However,the predisposing factors responsible in this particularinstance must remain speculative.

The adult literature indicates that it is bipolar pa­tients who, while on antidepressant medication, candevelop hypomania.6 For instance, a rece~t study byAkiskal and associates' of 100 patients with neuroticdepression distinguished primary depression fromnonprimary cases by the early occurrence of a "phar­macologic hypomania" in ten patients with primaryaffective disorder (nine bipolar and one unipolar).

The child described here, also receiving antidepres­sant medication, may in fact be a bipolar patient whosustained his first episode of hypomania at an un­usually young age. A close follow-up is planned inorder to document that. However, this case does repre­sent the first known report ofa hypomanic reaction in adepressed child. 0

Supported by NIH grant RR-00287-13 for the University ofMissouri General Clinical Research Center and Missouri In­stitute of Psychiatry. and Individual Research Fund grants5929-1/46 and 5929146 to Dr. Kashani.

REFERENCES1. Petit JM, Biggs JJ: Tricyclic antidepressant overdoses in adolescent

patients. Pediatrics 51:283-287, 1977.2. Frommer EA: Depressive illness in childhood, in Recent Developments in

Affective Disorders. spec publ no 2, Br J Psychiatry, pp 117-136, 1968.3. Lucas AR, Lockett HJ, Grimm F: Amitriptyline in childhood depressions.

Dis Nerv Syst, 28:105-110, 1965.4. Paykel ES, Coppen A: Psychopharmacology of Affective Disorders. New

York. Oxford University Press. 1979, p 130.5. Mielke DH: Adverse reactions of thymoleptics, in Gallant OM. Simpson GM

(ads): Depression: Behavioral. Biochemical. Diagnostic and TreatmentConcepts. New York. Spectrum. 1976. p 273.

6. Cole JO. Davis JM: Antidepressant drugs, in Freedman AM. Kaplan HI.Sadock BJ (eds): Comprehensive Textbook of Psychialry. Baltimore.Williams & Wilkins. 1975. vol 2. p 1946.

7. Akiskal HS, Rosenthal RH, Rosenthal TL, et al: Differentiation of primaryaffective illness from situational. symptomatic, and secondary depres­sions. Arch Gen Psychiatry 38:635-643. 1979.

PSYCHOSOMATICS