Letters

Visual Hallucinations tromcthorphan SIR: I would

After

Combining

like to report

the

Fluoxetine

occurrence

to the

and

of visual

Dcx-

halbuci-

nations in a patient treated with fluoxetine when she used a cough syrup containing dextromethorphan. To my knowledge, such interaction has not yet been reported in the literatune. Ms. A, a 32-year-old obese patient with a 20-year history of dysthymia, presented with manifestations of major depression. She complained of sadness and guilt, anhedonia, initial insomnia, and early morning wakening. She also cxpressed feelings of helplessness and hopelessness. A brief treatment trial with doxepin was terminated because of drowsiness and her fear of gaining more weight. A regimen of fluoxetine, 20 mg/day, was started. On the 1 7th day of treatment, Ms. A had symptoms of a common cold including congestion, runny nose, and cough. She took two teaspoonfuls of a cough syrup containing dextromethorphan. She had no prior side effects with that drug. The next morning, she took two more teaspoonfuls of the cough syrup with her fluoxetine capsule. Two hours later, she expenienced vivid hallucinations of bright colors and distortions of the shapes and dimensions of her surroundings. The hallucinations lasted 6-8 hours, then stopped. They were very similar to her past experience with LSD 12 years earlier. Fluoxetine was discontinued at Ms. A’s request. She also refused any other antidepressants. I continued to see her in therapy for another year, with some improvement, and without recurrence of the hallucinations. Fluoxetine is a specific serotonin (S-HT) reuptake inhibitor and dextromethorphan is an NMDA receptor antagonist related in its site of action to phencyclidine and ketamine (2). However, dextromethorphan does not have any known psychomimetic effects (3). It is known that S-HT2 receptors mediate the hallucinogenic effects of LSD (4). Also, there is some ( 1 ),

suggestion

of a functional

interaction

between

glutaminergic

and serotonergic pathways (5). An electronic literature search did not produce any reports of visual hallucinations caused by fluoxetine or dextromethorphan. The patient used each of the drugs alone without side effects. The hallucinations appeared only when both drugs were combined. This suggests a synergistic action of the drugs in this patient. “Flashbacks” or “post hallucinogen perception reaction” may be another cxplanation. However, the long duration of the hallucinations (6-8 hours) makes this conclusion unlikely.

REFERENCES 1. Bergstrom

macology

RF, Lemberger

L, Farid

and pharmacokinetics

NA, Wolen

of fluoxetine:

chiatry (Suppl) 1988; 3:47-50 2. Ferkany JW, Borosky SA, Clissold tromethorphan inhibits NMDA-induced macol 1988; 151:151-154

1406

RL: Clinical phara review. Br J Psy-

DB, Pontecorvo convulsions.

Mi: DcxEurJ Phar-

Editor

3. Musacchio

JM, Klein M, Carroll PD: Dextromethorphan, sigma receptors and the psychomimetic effects of sigma opiates. International Narcotic Research Conference (INRC), 1 989, pp 13-16 4. Sadzot B, Baraban JM, Glennon RA, Lyon RA, Leonhardt S,Jan CR, Titeler M: Hallucinogenic drug interactions at human brain S-HT2 receptors: implications for treating LSD-induced hallucinogenesis. Psychopharmacology (Ben) 1989; 98:495-499 S. Gandolfi 0, DallOlio R, Roncada P, Montanaro N: NMDA antagonists metabolism

interact with S-HT-stimulated and impair passive avoidance Neuroscience Lett 1990; 113:304-308 NAGUI

Acute Exacerbation Tryptophan Depletion

of Body

phosphatidylinositol retention in the rat.

S. ACHAMALLAH, Sacramento,

Dysmorphic

Disorder

M.D. Calif.

During

SIR: Recent literature has examined the relationship between body dysmorphic disorder and obsessive-compulsive disorder (1, 2). Serotonin reuptake inhibitors have been reported to be effective in treating both conditions (3). We report effects of acute tryptophan depletion in a patient with a history of major depression and obsessive-compulsive disorder who met DSM-III-R criteria for body dysmorphic disorden. The patient participated in an ongoing study of the effects of acute tryptophan depletion on mood and obsessive-compubsive symptoms in patients with obsessive-compulsive disorder treated with S-HT reuptake inhibitors.

Ms. A was a 42-year-old woman with a past history of major depression responsive to treatment with monoamine oxidase inhibitors (MAOIs). Most prominent throughout her course however, and unresolved with MAOI treatment, were obsessive concerns about hem face and appearance, which fulfilled criteria for body dysmorphic disorder. Picking and filing at perceived facial imperfections consumed hours at a time, leading to wounds and secondary infections. Five years prior to the study reported here she deveboped counting rituals and compulsions involving symmetry and exactness, which prompted the additional diagnosis of obsessive-compulsive disorder. Treatment with clomipramine, 200 mg/day, and buspirone, 60 mg/day, was associated with near elimination of picking and filing, leading to healing of her face and a normal appearance at the time of examination. The patient did continue to spend up to an hour a day examining her face and obsessing about its imperfections. Her other obsessive-compulsive symptoms mesolved completely. Compared with sham depletion under double-blind conditions, acute tryptophan depletion produced a dramatic exacerbation in her dysmorphophobia. She became afraid that people were looking at her face, turned away from the open door of the testing room, and made repeated trips to the bathroom to stare in the mirror. The patient also became extremely tearful, reporting, “I don’t know why I am crying all the time. I don’t have anything in particular to

Am

J

Psychiatry

1 49:1

0, October

1992

LETFERS

feel sad about.” nausea, without level of concern

Sham depletion produced only very mild change in the patient’s affective state or regarding her face.

Administration

of a low

tryptophan

diet

coupled

with

symptoms. sinus

ethynybestradiol had been taking

an

Laboratory

amino acid drink devoid of tryptophan has proven a safe and reliable method for producing lowered plasma tryptophan levels (4). Delgado et al. (4) have demonstrated the reemergence of depressive symptoms in depressed patients treated with

S-HT

reuptake

inhibitors

when

plasma

tryptophan

levels

(5).

studies

The exacerbation of both depression and body dysmorphic disorder associated with acute tryptophan depletion suggests that S-HT reuptake inhibitors used in the treatment of these syndromes share a common mechanism of action that depends upon the ongoing availability of S-HT. That Ms. A’s obsessive-compulsive symptoms were not exacerbated by tryptophan depletion is consistent with other preliminary mesuits of tryptophan depletion in patients with obsessive-cornpulsive

disorder

treated

et al., unpublished

with

S-HT

reuptake

inhibitors

(Barn

data).

REFERENCES 1. Phillips

KA: Body

ugliness.

AmJ

dysmorphic

Psychiatry

disorder:

1991;

2. Hollander E, Neville D, Decaria bowitz MR: On dysmorphophobia compulsive

disorder

(letter).

the distress

148:1138-1

of imagined

149

C, Mullen L, Schneier FR, Liemisdiagnosed as obsessive-

Psychosomatics

1990;

31:468-469

3. Hollander Treatment blockers. 4. Delgado Heninger

E, Liebowitz MR, Winchel R, Klumker A, Klein DF: of body dysmorphic disorder with serotonin reuptake Am J Psychiatry 1989; 146:768-770 PL, Charney DS, Price LH, Aghajanian GK, Landis H, GR: Serotonin function and the mechanism of antidepressant action. Arch Gen Psychiatry 1990: 47:411-418 S. Maj J, Lewandowska A: Central serotonin mimetic action of phenylpiperazines. Pol J Pharmacol Pharm I 990; 32:495-504 LINDA C. BARR, M.D. WAYNE K. GOODMAN, M.D. LAWRENCE H. PRICE, M.D. New Haven, Conn.

of Estrogens

on Thyroid

Function

thought to exert rather minor actions function, yet the literature concerning on thyroid function has provided con-

flicting

Oral

results

(1,

2).

estrogens

are

known

to increase

synthesis of thyroid binding globulin with a consequent rise in T4 and T3, yet plasma concentrations of free T4 and T3 remain unchanged. Frank hyperthyroidism has not been descnibed in association with estrogen use, yet the following is a case in which some symptoms typical of hyperthyroidism resolved after discontinuation of oral estrogens, corresponding with normalization in thyroid function tests.

ized

in the

roid

Am

J

Psychiatry

1 49;1

0, October

1992

0.05 mg/norethindrone regularly for I year results

were

normal

physical only

finding

was

medication

was

1 mg, which on a 28-day cycle. except

for the

she

following

absence

of exogenous

estrogen.

This

is the

first

function,

and

about

50%

of these

patients

had

a sponta-

neous normalization of values in 2 weeks (4). Although direct cause of symptoms is not unequivocal, this case serves to expand the data regarding endocrine-associated psychiatric symptoms and aids the clinician in treating patients with psychiatric complaints who are using oral contraceptives.

REFERENCES SH, Braverman

LE (eds): Werner’s

the Thyroid:

A Funda-

mental and Clinical Text. Philadelphia, Lippincott, 1986 Gross HA: Effects of biologically active steroids on thyroid tion in man. J Clin Endocrinol Metab I 971 ; 33:242-248

3. Leigh H, Kramer SI: The psychiatric manifestations disease. Adv Intern Med I 984; 29:423-445 4. Cohen

patients.

KL, Swiger ME: Thyroid function JAMA 1979; 242:254-257

screening

Bupropion-Induced

12-year pression

Carbohydrate

Craving

in psychiatric

and Weight

letter reports the case of a 44-year-old history of chronic pain and accompanying of relatively recent onset.

func-

of endocrine

BRIAN A. FARAH, Winston-Salem,

SIR: This

Ms. A, a 21-year-old woman, presented with a chief cornplaint of, “I just can’t stop crying.” She had an 8-month history of crying episodes that had increased in frequency and duration, making her unable to work or interact with those outside her family. Psychosocial stressoms were minimal; she denied feelings of sadness and neumovegetative

her

reported case that entertains the possibility of estrogens affecting behavior through alterations in thyroid function. Estrogens have been demonstrated to alter levels of TSH in vivo (2). However, evidence that the thyroid function test results may have been incidental is provided by Cohen’s study in which 1 8% of adult psychiatric inpatients had abnormal thy-

2.

SIR: Estrogens are upon intrinsic thyroid the effects of estrogens

her only bpm);

Mood changes associated with oral contraceptive use are webb documented; 60% of oral contraceptive users report some degree of affective symptoms, and 10% will discontinue their use due to depression or irritability (3). Our patient had a marked elevation in T4 on presentation, atypical for estrogen use, and symptoms resolved as thyroid function tests normal-

I . Ingbar Effect

(120

EDITOR

thyroid function tests: thyroid-stimulating hormone (TSH)=1.4 j.tU/ml (normal=0.S-4.S liU/mb); T4=17.4 jtg/dl (5.5-11.8 ig/dl); T3 uptake=31.2% (35.9%-43.S%); and free T4 index (F11)=S.4 (2.3-5.23). Estrogen was discontinued, and 2 weeks later, thyroid function tests were largely unchanged (T4 was 14.8 tg/dl). There was little improvement in symptoms. Four weeks after discontinuation, crying spells were reduced by 50% (1-3 per 2 days), pulse was 100 bpm, and thyroid function tests were as follows: TSH=1.9 tU/ml, T4=13.1 tg/dl, T3 uptake=32.9%, and fll=4.31. Finally, 2 months after discontinuation, Ms. A was free of crying spells, thyroid function tests were normal (TSH=1.3 jiU/ml, T4=11.8 ig/dl, T3 uptake=36.6%, and F11=4.2S), pulse was 82 bpm, and she was completely functional.

are acutely lowered in this manner. This effect is presumably mediated through a reduction in brain S-HT, as decreases in plasma tryptophan have been shown to reduce brain S-HT in preclinical

On presentation,

tachycardia

THE

TO

M.D. N. C.

Gain

man with a major de-

Mr. A was seen in an outpatient pain clinic and found to suffer from recurrent major depression of approximately 4-month duration. The patient, in addition to displaying

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