210
BIOL PSYCHIATRY
Correspondence
1992;32:207-213
11.05 +- 6.94 and in SA = 20.00 - 20.94; t = 1.15, p = 0.27), There were no significant differences between cortisol responses (main effect for group: F = 0.01, df = 1,14, p = 0.93; group x time: F = 1.26, df = 6,9, p = 0.36)or prolactin responses (main effect for group: F = 0.27, df = 1,14, p = 0.61; group x time: F = 0.48, df = 6,9, p = 0,81). Behavioral responses were also not significantly different. This preliminary study found similar MCPP-induced cortisol, prolactin, and behavioral respoases in suicide attempters and healthy controls. These results suggest that 5-HT receptor sensitivity in suicide attempters is not different from that of healthy subjects. Our results contrast with previous chal,. lenge studies in similar populations indicating blunted prolactin responses to feafluramine (Coccaro et al 1989) and increased cortisol response to 5-HTP (Mcltzer et al 1984). However, the mechanism of action of MCPP is different from these other challenge agents (Kahn and Wetzler 1991), making comparisons between studies difficult. Moreover, the sample size was small and there was large individual variability in MCPP blood levels. There was also a predominance of non-violent suicide attempts in our study and biological abnormalities may be less pronounced in these individuals. Future research with larger samples is required to explain these discrepant results. Our study was funded in part by the NIMH grant i RO3 MH451119, and by American Suicide Foundation.
Exercise and Antidepressant Serum Levels To the Editor: I wish to call attention to the effects of strenuous exercise (running 2-5 miles) on serum levels of desipramine and arnitriptyline in two psychiatric outpatients. Blood was drawn immediately before, immediately after, and 1 hr after running. Drug levels were analyzed using gas-chromatographic mass spectrometry (GCMS). This analytic technique is known
Martin L. Korn Gregory Asnis Serena-Lynn Brown Herman V. van Praag Dept of Psychiatry Einstein College of Medicine Bronx NY 10461
References Coccaro EF, Siever L J, Klar HM, Maurer G, Coehrane K, Cooper T, Mohs RC, Davis KL (1989): Serotonergie studies in patients with affective and personality disorders: Correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry 46:587-599. Kahn RS, Asnis GM, Wetzler S, van Praag HM (t 988): Neuroendocrine evidence for serotonin receptor hypersensitivity in patients with panic disorder. Psychopharmacol 96:360-364. Meltzer HY, Umberkoman-Wiita B, Roberston A, Trico BJ, Lowy M, Perline R (1984): Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. Arch Gen Psychiatry 41:366-374. van Praag, HM ( 1988): Serotonergic mechanisms and suicidal behavior. Psychiatry & Psychobiol 3:335346. Kahn RS, Wetzler S ( 199 !). m-Chlorophenylpiperazine as a probe of serotonin receptors: a review, Bio Psychiatry 30:1139-1166.
to be highly sensitive and selective, in addition, serum osmolality was measured. Patients were allowed to drink and eat after the post-running sample was drawn. Both patients wcre in steady-state conditions and took their last dose |2 hr betore me baseline evaluation. Ms. A was a 26.year-old female with a diagnosis of recurrent major depressive disorder who had been taking desipramine 150 mg a day at bedtime. Her pre-running desipramine level was 89 ng/ml and serum osmolality was 282 mos/kg. After running her desipramine level had increased by 10% to 98 ng/ml
Correspondence
BIOL PSYCHIATRY 1992;32:207-213
2i 1
and her osmolality by 5.7% to 298 mos/kg. After 1 hr the desipramine level had declined to 81 ng/ml and the osmolality to 289 mos/kg. Ms. B was a 22-year-old female with a diagnosis of dysthymia and non-purging bulimia nervosa who had been taking amitriptyline 150 mg a day at bedtime. The combined serum levels of amitriptyline and nortriptyline increased from 101 ng/ml to 116 ng/ml after running (14.9%), and fell again to 94 ng/ml I hr after the exercise was stopped. All of these total tricyclie levels consisted of approximately equal parts of amitdptyline and nortriptyline. Serum osmolality remained almost stable with 285 mos/kg pre-running, 298 mos/kg immediately after (increase of 2.1%), and 286 mos/kg i nr after running. In both patients a moderate increase of antidepressant serum levels occurred after running : 10% and 14.9%, respectively. This is outside the withinday coefficients of variation, which are 4%-6% for these drugs using GCMS. One hour after exercise was stopped, and after the patients were allowed to eat and drink, the increase had disappeared. It is possible that exercise may reduce the volume of distribution of the drugs through changes in blood flow, plasma protein and tissue binding, temperatuce, and pH changes (Van Baak, 1990). The slight increase of serum osmolality (5.7% and 2.1%, respectively) due to loss of sweat during exercising might
in part explain this phenomenon, because this leads to increased protein binding of drugs. However, only "free" (unbound) drug is in equilibrium with tissue and therefore biologically active. The exact mechanism of the change in volume distribution after exercising remains unclarified. Whereas our results emphasize the importance of controlling physical activity in pharmacokinetic studies, the practical consequences are far less clear. The results seem to suggest that short-term strenuous exercise does not ir,crease tricyclic serum levels to a degree that is clinically significant. Further studies are warranted to investigate the effect of long-term exercise on antidepressant serum levels.
Herpes Simplex Mimicking Functional Psychosis
echolalia and perseveration. On admission her blood pressure (BP)was 160/100. Erythrocyte sedimentation rate (ESR) was 21 with a normal white count. All other blood tests, including cultures, were unremarkable. Pregnancy test was negative. CxR was normal. Brain computed tomography (CT) was normal. An electroencephalogram (EEG) was inconclusive due to her physical agitation. A complicating factor on admission was the presence of a large abdominal mass. An abdominal ultrasound 3 months earlier had suggested that this was an ovarian cyst. A recommended laparotomy was never done. On admission, clinical examination showed the mass to have grown somewhat. A repeat ultrasound had to be abandoned again due to her extreme agitation despite 30 mg of haloperidol QDS.
To the Editor: It is unusual for a case of encephalitis to present to a psychiatric service. Nonetheless, it does occur, and Lishman, in his classic text Organic Psychiatry, says, "Special interest attaches to the occasional cases which present with psychiatric disorder." A 31-year-old Ghanaian woman was admitted to an acute psychiatric ward in a London teaching hospital following referral by her general practitioner. She was accompanied by her husband, an educated man, who provided mush of the history. She presen:ed with visual hallucinations, paranoia, and a 3week history of headaches. She exhibited marked
Martina de Zwaan Dept. of Psychiatry University of Vienna Wahringer Gtirtel, 8-20 1090 Vienna, Austria
References Van Baak (1990): Influence of exercise on the pharmacokinetic of drugs. Clin Ph~wmacokinet19:3243.
BIOL PSYCHIATRY
Correspondence
1992;32:207-213
11.05 +- 6.94 and in SA = 20.00 - 20.94; t = 1.15, p = 0.27), There were no significant differences between cortisol responses (main effect for group: F = 0.01, df = 1,14, p = 0.93; group x time: F = 1.26, df = 6,9, p = 0.36)or prolactin responses (main effect for group: F = 0.27, df = 1,14, p = 0.61; group x time: F = 0.48, df = 6,9, p = 0,81). Behavioral responses were also not significantly different. This preliminary study found similar MCPP-induced cortisol, prolactin, and behavioral respoases in suicide attempters and healthy controls. These results suggest that 5-HT receptor sensitivity in suicide attempters is not different from that of healthy subjects. Our results contrast with previous chal,. lenge studies in similar populations indicating blunted prolactin responses to feafluramine (Coccaro et al 1989) and increased cortisol response to 5-HTP (Mcltzer et al 1984). However, the mechanism of action of MCPP is different from these other challenge agents (Kahn and Wetzler 1991), making comparisons between studies difficult. Moreover, the sample size was small and there was large individual variability in MCPP blood levels. There was also a predominance of non-violent suicide attempts in our study and biological abnormalities may be less pronounced in these individuals. Future research with larger samples is required to explain these discrepant results. Our study was funded in part by the NIMH grant i RO3 MH451119, and by American Suicide Foundation.
Exercise and Antidepressant Serum Levels To the Editor: I wish to call attention to the effects of strenuous exercise (running 2-5 miles) on serum levels of desipramine and arnitriptyline in two psychiatric outpatients. Blood was drawn immediately before, immediately after, and 1 hr after running. Drug levels were analyzed using gas-chromatographic mass spectrometry (GCMS). This analytic technique is known
Martin L. Korn Gregory Asnis Serena-Lynn Brown Herman V. van Praag Dept of Psychiatry Einstein College of Medicine Bronx NY 10461
References Coccaro EF, Siever L J, Klar HM, Maurer G, Coehrane K, Cooper T, Mohs RC, Davis KL (1989): Serotonergie studies in patients with affective and personality disorders: Correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry 46:587-599. Kahn RS, Asnis GM, Wetzler S, van Praag HM (t 988): Neuroendocrine evidence for serotonin receptor hypersensitivity in patients with panic disorder. Psychopharmacol 96:360-364. Meltzer HY, Umberkoman-Wiita B, Roberston A, Trico BJ, Lowy M, Perline R (1984): Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. Arch Gen Psychiatry 41:366-374. van Praag, HM ( 1988): Serotonergic mechanisms and suicidal behavior. Psychiatry & Psychobiol 3:335346. Kahn RS, Wetzler S ( 199 !). m-Chlorophenylpiperazine as a probe of serotonin receptors: a review, Bio Psychiatry 30:1139-1166.
to be highly sensitive and selective, in addition, serum osmolality was measured. Patients were allowed to drink and eat after the post-running sample was drawn. Both patients wcre in steady-state conditions and took their last dose |2 hr betore me baseline evaluation. Ms. A was a 26.year-old female with a diagnosis of recurrent major depressive disorder who had been taking desipramine 150 mg a day at bedtime. Her pre-running desipramine level was 89 ng/ml and serum osmolality was 282 mos/kg. After running her desipramine level had increased by 10% to 98 ng/ml
Correspondence
BIOL PSYCHIATRY 1992;32:207-213
2i 1
and her osmolality by 5.7% to 298 mos/kg. After 1 hr the desipramine level had declined to 81 ng/ml and the osmolality to 289 mos/kg. Ms. B was a 22-year-old female with a diagnosis of dysthymia and non-purging bulimia nervosa who had been taking amitriptyline 150 mg a day at bedtime. The combined serum levels of amitriptyline and nortriptyline increased from 101 ng/ml to 116 ng/ml after running (14.9%), and fell again to 94 ng/ml I hr after the exercise was stopped. All of these total tricyclie levels consisted of approximately equal parts of amitdptyline and nortriptyline. Serum osmolality remained almost stable with 285 mos/kg pre-running, 298 mos/kg immediately after (increase of 2.1%), and 286 mos/kg i nr after running. In both patients a moderate increase of antidepressant serum levels occurred after running : 10% and 14.9%, respectively. This is outside the withinday coefficients of variation, which are 4%-6% for these drugs using GCMS. One hour after exercise was stopped, and after the patients were allowed to eat and drink, the increase had disappeared. It is possible that exercise may reduce the volume of distribution of the drugs through changes in blood flow, plasma protein and tissue binding, temperatuce, and pH changes (Van Baak, 1990). The slight increase of serum osmolality (5.7% and 2.1%, respectively) due to loss of sweat during exercising might
in part explain this phenomenon, because this leads to increased protein binding of drugs. However, only "free" (unbound) drug is in equilibrium with tissue and therefore biologically active. The exact mechanism of the change in volume distribution after exercising remains unclarified. Whereas our results emphasize the importance of controlling physical activity in pharmacokinetic studies, the practical consequences are far less clear. The results seem to suggest that short-term strenuous exercise does not ir,crease tricyclic serum levels to a degree that is clinically significant. Further studies are warranted to investigate the effect of long-term exercise on antidepressant serum levels.
Herpes Simplex Mimicking Functional Psychosis
echolalia and perseveration. On admission her blood pressure (BP)was 160/100. Erythrocyte sedimentation rate (ESR) was 21 with a normal white count. All other blood tests, including cultures, were unremarkable. Pregnancy test was negative. CxR was normal. Brain computed tomography (CT) was normal. An electroencephalogram (EEG) was inconclusive due to her physical agitation. A complicating factor on admission was the presence of a large abdominal mass. An abdominal ultrasound 3 months earlier had suggested that this was an ovarian cyst. A recommended laparotomy was never done. On admission, clinical examination showed the mass to have grown somewhat. A repeat ultrasound had to be abandoned again due to her extreme agitation despite 30 mg of haloperidol QDS.
To the Editor: It is unusual for a case of encephalitis to present to a psychiatric service. Nonetheless, it does occur, and Lishman, in his classic text Organic Psychiatry, says, "Special interest attaches to the occasional cases which present with psychiatric disorder." A 31-year-old Ghanaian woman was admitted to an acute psychiatric ward in a London teaching hospital following referral by her general practitioner. She was accompanied by her husband, an educated man, who provided mush of the history. She presen:ed with visual hallucinations, paranoia, and a 3week history of headaches. She exhibited marked
Martina de Zwaan Dept. of Psychiatry University of Vienna Wahringer Gtirtel, 8-20 1090 Vienna, Austria
References Van Baak (1990): Influence of exercise on the pharmacokinetic of drugs. Clin Ph~wmacokinet19:3243.
