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Treatment of crack-cocaine-induced compulsive behavior with trazodone
Journal of Substance Abuse Treatment, Vol. 12, No. 2, pp. 85-88, 1995 Copyright © 1995 Elsevier Science Ltd Printed in the USA. All rights reserved 0740-5472/95 $9.50 + .00
Pergamon
0740-5472(95)00001-1
ARTICLE
Treatment of Crack-Cocaine-Induced Compulsive Behavior With Trazodone HANI RAOUL KHOUZAM, MD, M P H , * ~ § MICHAEL F. MAYO-SMITH, MD, MPH,*§ DONALD R . BERNARD, MD,*§ AND JACK A . MAHDASIAN, MD~" *VA Medical Center, Manchester, New Hampshire; -~Dartmouth Medical School, Lebanon, New Hampshire; :~Department of Psychiatry and Behavioral Sciences, Universityof Oklahoma, College of Medicine, Oklahoma City, Oklahoma; §Harvard Medical School, Boston, Massachusetts
Abstract-Foraging is a compulsive behavior o f searching f o r pieces o f crack cocaine that the individual believes might have been accidentally misplaced. Three clinical cases o f compulsive foraging behavior associated with crack cocaine are described. Due to the development o f side effects secondary to the antidepressant desipramine, the patients were switched to the antidepressant trazodone. The use o f trazodone led to remission o f the foraging behavior. The authors hypothesize this remission was due to trazodone serotonin reuptake inhibitory action. In all three cases, the patients did not relapse into abusing crack cocaine.
Keywords-crack; cocaine; foraging; pharmacotherapy; trazodone.
CHRONIC USE OF stimulants has been associated with "stereotyped examining, searching, and sorting behaviors," which have been referred to as "obsessivecompulsive tendencies" (EUinwood, Sudilovsky, & Nelson, 1973). The emergence of "senseless repetitive gestures or tasks" has also been reported in some patients who abuse cocaine (Brady, Lydiard, Malcolm, & Ballenger, 1991). Some patients who abuse crack cocaine commonly describe a compulsive searching for pieces of crack cocaine that they believe might have been accidentally dropped or misplaced by someone in the area where they smoked the crack. Studies have reported that as many as 50°70-80% of patients abusing crack cocaine develop such behavior (Brady et al., 1991; Rosse et al., 1993).
In this report, the authors describe successful trazodone treatment for three patients who developed compulsive foraging behavior secondary to abusing crack cocaine.
CASE REPORTS
Patient A A 39-year-old White male presented to the emergency room (ER) complaining o f fears of "losing his mind" and "going crazy." The patient reported being unable to stop searching for pieces of crack cocaine that he might have accidentally dropped on the carpet in the room where he had been smoking the crack. The patient was distressed because he knew there was no pieces of crack cocaine on the carpet but could not stop himself from picking through the carpet's pile. In addition to using cocaine, he had a history of abusing alcohol, heroin, and marijuana. For the last 2 months
The authors thank Ms. Susan E. Field and Ms. BerylCase Leggett for their help and assistance. Requests for reprints should be addressed to Dr. Hani R. Khouzam, VA Medical Center, 718 Smyth Road, Manchester, NH 03104-4098. _ k
Received February 16, 1994; First Revision October 5, 1994; Second Revision December 6, 1994; Accepted December 7, 1994. 85
86
he had been smoking crack cocaine from 4 to 6 hr a day, using up to 3 grams every day. Physical examination and laboratory tests including electrolytes, complete blood count (CBC), urine analysis (UA), electrocardiogram (ECG), chest x-ray (CXR), and thyroid function tests (TFT) were all normal. A urine drug screen was negative for alcohol, opiates, and cannabis but positive for cocaine metabolites. Mr. A was admitted to the inpatient substance abuse treatment program (SATP). To decrease his cocaine craving, Mr. A was given desipramine in a daily divided dose of 150 mg. Desipramine did initially decrease the intensity of the craving (Gawin et al., 1989). However it did not decrease his behavior of constantly searching for crack cocaine on carpeted floors, the furniture, and in the bathrooms. After being on desipramine for 1 week, Mr. A developed urinary hesitancy (Pollack & Rosenbaum, 1987), and he asked that it be discontinued. Because he complained of persistent insomnia, he was given trazodone 50 mg at bedtime. This improved his sleep (Montgomery, Oswald, Morgan, & Adam, 1983), and he also noticed that it decreased his anxious feelings (Liebowitz, & E1-Mallakh, 1989) during the day. His dose was gradually increased up to 200 mg daily given at bedtime. Two weeks following the beginning of treatment with trazodone, the compulsive foraging behavior of searching for crack cocaine subsided. Mr. A was discharged from the SATP to the outpatient rehabilitation program. During a follow-up period of 3 months, foraging behavior did not re-emerge. The patient was compliant with taking 200 mg of trazodone daily, and he continued to abstain from crack cocaine. Patient B
A 27-year-old White female presented to the psychiatry crisis center complaining of inability to control her urges "of constantly checking her clothes for pieces of crack cocaine." Ms. B had never abused any alcohol or other drugs and did not have any prior medical or psychiatric illnesses. Ms. B smoked crack for the first time 3 months ago and at the time of presentation had been smoking up to 2 grams o f crack daily. For the 4 weeks prior to admission, she began repeatedly checking her clothes, shoes, pockets, and socks hoping to find pieces of crack cocaine. One week prior to admission, she developed severe cravings and as a result would leave her desk at work approximately every half hour and sneak to the restroom to smoke crack. If she could not smoke the crack, she would engage in the ritualistic behavior of constantly checking her clothes for pieces o f crack cocaine. Ms. B took a leave of absence from her job and became increasingly fearful of leaving her house due to the inability to control the intense urges o f constantly checking her clothes. Although she had never had any episode of
H . R . K h o u z a m et al.
indecent behaviors, she worried about being arrested if she took her clothes off in public to check for pieces of crack. Ms. B was referred from the crisis center and admitted to the SATP. Physical examination and laboratory tests including electrolytes, CBC, UA, TFT, CXR, and ECG were normal. Urine drug screen was positive for cocaine metabolites but negative for other drugs of abuse. Treatment began with bromocriptine 0.625 mg q.i.d. (Giannini & Billet, 1987). However, Ms. B continued to experience cravings for the crack, so she was started on desipramine (Gawin et al., 1989) 25 mg daily, which was gradually increased to 150 mg divided dose daily over a 14-day period. Desipramine did alleviate the severe cravings, but the compulsive foraging behavior of constantly checking the clothes for crack intensified. When desipramine was tapered down and finally discontinued, Ms. B experienced persistent difficulty with falling asleep. Trazodone was initiated at a dose of 50 mg at bedtime (Montgomery et al., 1983). Over the following 5 days, trazodone was gradually increased, and finally, at a bedtime dose of 200 mg, the insomnia subsided. Ms. B did not report any side effects due to the trazodone and was surprised to notice that after being on the 200-mg dose for 10 days her urges to constantly check her clothes for pieces of crack subsided. Ms. B requested to be maintained on trazodone at the same 200-mg daily bedtime dose. This was done, and 6 months following her discharge from the SATP, the patient continued to abstain from abusing crack and did not relapse into the compulsive foraging behavior. Patient C
A 35-year-old African-American male with documented history of hypertension was brought to the ER by his wife following an episode of severe headache that started early on that morning. Mr. C's past history included noncompliance with treatment for hypertension and a pattern of daily abuse of alcohol and crack cocaine over the last 9 months. The patient's blood pressure upon arrival at the ER was 209/119 mmHg. His blood pressure was treated, and he was admitted to the SATP for cocaine abuse treatment. Physical examination, electrolytes, CBC, UA, TFT, CXR, and ECG were all normal. During his first week of rehabilitation treatment, Mr. C did not report cravings for cocaine. With the beginning of the second week, the nursing staff observed Mr. C constantly checking the window sill in his room. When he was asked about the purpose of his checking, he acknowledged that he was searching for pieces of crack cocaine. During a treatment team evaluation meeting, Mr. C admitted being totally helpless toward stopping his behavior of checking the window sill in search for pieces of crack cocaine despite knowing that his search was in vain. Mr. C was started on desipramine (Ga-
Treatment of Compulsive Behavior With Trazodone
win et al., 1989), 25 mg a day, which was gradually increased to 150 mg divided daily dose over a 15-day period. Mr. C developed an agitated response to desipramine (Roehrich & Gold, 1991), so it was discontinued and trazodone initiated at a dose of 50 mg three times daily (Louie, Lannon, & Ketler, 1989). Mr. C did not report any side effects of trazodone. Three weeks after initiation of trazodone treatment, the foraging behavior of constantly checking the window sills for pieces of crack cocaine subsided. Mr. C was discharged from the SATP and was followed by the outpatient rehabilitation program. He was maintained on trazodone 150 mg daily in divided doses. During a 3-month follow-up period, he remained compliant with the trazodone treatment and did not relapse into abusing crack cocaine. His foraging behavior has not reemerged, and he has remained abstinent from alcohol and compliant with medical follow-up for hypertension. Mr. C also became spiritually involved and did report the following verse: "I am free from the power of cocaine and God's benefits to me include holiness and everlasting life" (paraphrasing Romans, 6:22) as an important factor in his recovery.
DISCUSSION Cocaine is usually used in binges of a few hours to a week. When a patient stops, or "crashes," craving may persist for a few hours, but for the next 3-5 days, fatigue, depression, increased sleep, and increased appetite may occur. This stage has been called Phase 1 (Gawin et al., 1989) and has low risk of relapse. Over the next 1-10 weeks, the patient progresses from feeling euthymic with mild cocaine craving to a state of high craving with anhedonia, anergia, and dysphoria. If the patient gets through this stage, called Phase 2, then craving becomes only occasional although it can be triggered by conditioned cues like objects, places, or environmental stimuli similar to the scenes where cocaine was used. Several pharmacotherapies have been tried in Phase l, including bromocriptine (Giannini & Billet, 1987) and amantadine (Tennant & Sagherian, 1987), but with little obvious efficacy in controlled trials (Michels & Marzuk, 1993). Desipramine has been shown to be somewhat effective in reducing dysphoria and craving in Phase 2 (60O7o abstinence in desipramine patients vs. 17°7oabstinence on placebo; Gawin et al., 1989). Other antidepressants might do as well, but desipramine was chosen because of its predominant norepinephrine (NE) effect and its relatively good side-effect profile (Schatzberg & Cole, 1991). For the more prolonged Phase 3, which begins after 6 weeks of abstinence and can last for months or years, controlled trials have not been performed (Michels & Marzuk, 1993).
87
The three patients described here did not tolerate desipramine side effects. Trazodone treatment was initiated for symptomatic relief of insomnia (in Patients A and B) and agitation (in Patient C). After the trazodone was initiated, a dramatic resolution of the foraging behavior was observed. However, as this was not a controlled study, we cannot determine if this resolution was just incidental due to the passage of time or the result of trazodone-specific pharmacological actions. The pharmacology of the antidepressant trazodone is complex and in some ways resembles that of the tricyclic antidepressants, the benzodiazepines, and the phenothiazines. However, the overall pharmacologic profile of trazodone differs from each of these classes of medications. The precise mechanism of action of trazodone is unclear, but it has been shown to selectively block the reuptake of serotonin 5-hydroxytryptamine at the presynaptic neuronal membrane. Thus, the central nervous system (CNS) effects of serotonin are potentiated. Trazodone does not appear to influence the reuptake of dopamine (DA) or NE within the CNS. The sedative effect of trazodone is thought to result from central alpha 1-adrenergic blocking activity. Although the exact mechanism of action has not been determined, trazodone also possesses significant anxiolytic properties (Liebowitz & EI-Mallakh, 1989). In these three patients, the development of the compulsive foraging behavior did not seem to be a consequence of intense craving for crack cocaine but a possible drug-induced type of compulsion (Rosse et al., 1993). Abnormality of crack serotonergic neural transmission has been implicated in obsessive-compulsive disorder (OCD) and cocaine abuse (Rosse et al., 1993). Because these three patients did not have a prior history of OCD, one could speculate that cocaine-induced foraging behavior might represent a drug-induced type of compulsive disorder. Serotonergic receptor supersensitivity could be a neurochemical substrate for postcocaine compulsive behaviors and consequently contribute to relapse and inability to maintain abstinence. Although obsessive compulsive symptomatology is associated with adverse mood states (Farid, 1986), none of the three patients had an underlying mood disorder prior to abusing crack cocaine. It appears that if, in fact, trazodone was contributing to the remission, this was not due to its antidepressant effects but rather a result of its antiobsessional properties (Hermesh, Aizenberg, & Munitz, 1990). In conclusion, these three cases support the concept that serotonin may be involved in mediating a crackcocaine-induced compulsive foraging behavior. Trazodone as a selective serotonin reuptake inhibitor (SSRI) as well as other SSRI such as fluoxetine, sertraline, paroxetine, and fluvoxamine could be efficacious pharmacotherapies for the treatment of the compulsive foraging behavior. However, we feel these cases
88
H.R. Khouzam et al.
represent interesting observations only, and this hypothesis needs further testing in well-designed placebocontrolled randomized trials. REFERENCES Brady, K.T., Lydiard, R.B., Malcolm, R., & Ballenger, J.C. (1991). Cocaine-induced psychosis. Journal of Clinical Psychiatry, 52, 509-512. Ellinwood, E.H., Jr., Sudilovsky, A., & Nelson, L.M. (1973). Evolving behavior in the clinical and experimental amphetamine (model) psychosis. American Journal of Psychiatry, 130, 10881093. Farid, B.T. (1986). Obsessional symptomatology and adverse mood states. British Journal of Psychiatry, 149, 108-112. Gawin, F.H., Kleber, H.D., Byck, R., Rounsaville, B.J., Kosten, T.R., Jatlow, P.I., & Morgan, C. (1989). Desipramine facilitation of initial cocaine abstinence. Archives of General Psychiatry, 46, 117-121. Giannini, A.J., & Billet, T.S. (1987). Bromocriptine-desipramine protocol in cocaine detoxification. Journal of Clinical Pharmacology, 27, 549-556. Hermesh, H., Aizenberg, D., & Munitz, H. (1990). Trazodone treatment in clomipramine-resistant obsessive compulsive disorder. Clinical Neuropharmacology, 13, 322-328. Liebowitz, N.R., & EI-Mallakh, R.S. (1989). Trazodone for the treatment of anxiety symptoms in substance abusers. Journal of Clinical Psychopharmacology, 9, 449-450.
Louie, A.K., Lannon, R.A., & Ketter, T.A. (1989). Treatment of cocaine-induced panic disorder. American Journal of Psychiatry, 146, 40-44. Michels, R., & Marzuk, P.H. (1993). Progress in psychiatry. The New England Journal of Medicine, 329, 628-638. Montgomery, I., Oswald, I., Morgan, K., & Adam, K. (1983). Trazodone enhances sleep in subjective quality but not in objective duration. British Journal of Clinical Pharmacology, 16, 139-144. Pollack, M.H., & Rosenbaum, J.F. (1987). Management of antidepressant-induced side effects. Journal of Clinical Psychiatry, 48, 3-8. Roehrich, H., & Gold, M.S. (1991). Cocaine. In D.A. Ciraulo & R.I. Shader (Eds.), Clinical manual of chemical dependence (pp. 195-231). Washington, DC: American Psychiatric Press, Inc. Rosse, R.B., Fay-McCarthy, M., Collins, J.P., Jr., Risher-Flowers, D., Alim, T.N., & Deutsch, S.I. (1993). Transient compulsive foraging behavior associated with crack cocaine use. American Journal of Psychiatry, 150, 155-156. Schatzberg, A.F., & Cole, J.O. (1991). Manual ofclinicalpsychopharmacology (2nd ed.). Washington, DC" American Psychiatric Press, Inc. Tennant, F.S., & Sagherian, A.A. (1987). Double-blind comparison of amantadine and bromocriptine for ambulatory withdrawal from cocaine dependence. Archive of Internal Medicine, 147, 109-112.
Pergamon
0740-5472(95)00001-1
ARTICLE
Treatment of Crack-Cocaine-Induced Compulsive Behavior With Trazodone HANI RAOUL KHOUZAM, MD, M P H , * ~ § MICHAEL F. MAYO-SMITH, MD, MPH,*§ DONALD R . BERNARD, MD,*§ AND JACK A . MAHDASIAN, MD~" *VA Medical Center, Manchester, New Hampshire; -~Dartmouth Medical School, Lebanon, New Hampshire; :~Department of Psychiatry and Behavioral Sciences, Universityof Oklahoma, College of Medicine, Oklahoma City, Oklahoma; §Harvard Medical School, Boston, Massachusetts
Abstract-Foraging is a compulsive behavior o f searching f o r pieces o f crack cocaine that the individual believes might have been accidentally misplaced. Three clinical cases o f compulsive foraging behavior associated with crack cocaine are described. Due to the development o f side effects secondary to the antidepressant desipramine, the patients were switched to the antidepressant trazodone. The use o f trazodone led to remission o f the foraging behavior. The authors hypothesize this remission was due to trazodone serotonin reuptake inhibitory action. In all three cases, the patients did not relapse into abusing crack cocaine.
Keywords-crack; cocaine; foraging; pharmacotherapy; trazodone.
CHRONIC USE OF stimulants has been associated with "stereotyped examining, searching, and sorting behaviors," which have been referred to as "obsessivecompulsive tendencies" (EUinwood, Sudilovsky, & Nelson, 1973). The emergence of "senseless repetitive gestures or tasks" has also been reported in some patients who abuse cocaine (Brady, Lydiard, Malcolm, & Ballenger, 1991). Some patients who abuse crack cocaine commonly describe a compulsive searching for pieces of crack cocaine that they believe might have been accidentally dropped or misplaced by someone in the area where they smoked the crack. Studies have reported that as many as 50°70-80% of patients abusing crack cocaine develop such behavior (Brady et al., 1991; Rosse et al., 1993).
In this report, the authors describe successful trazodone treatment for three patients who developed compulsive foraging behavior secondary to abusing crack cocaine.
CASE REPORTS
Patient A A 39-year-old White male presented to the emergency room (ER) complaining o f fears of "losing his mind" and "going crazy." The patient reported being unable to stop searching for pieces of crack cocaine that he might have accidentally dropped on the carpet in the room where he had been smoking the crack. The patient was distressed because he knew there was no pieces of crack cocaine on the carpet but could not stop himself from picking through the carpet's pile. In addition to using cocaine, he had a history of abusing alcohol, heroin, and marijuana. For the last 2 months
The authors thank Ms. Susan E. Field and Ms. BerylCase Leggett for their help and assistance. Requests for reprints should be addressed to Dr. Hani R. Khouzam, VA Medical Center, 718 Smyth Road, Manchester, NH 03104-4098. _ k
Received February 16, 1994; First Revision October 5, 1994; Second Revision December 6, 1994; Accepted December 7, 1994. 85
86
he had been smoking crack cocaine from 4 to 6 hr a day, using up to 3 grams every day. Physical examination and laboratory tests including electrolytes, complete blood count (CBC), urine analysis (UA), electrocardiogram (ECG), chest x-ray (CXR), and thyroid function tests (TFT) were all normal. A urine drug screen was negative for alcohol, opiates, and cannabis but positive for cocaine metabolites. Mr. A was admitted to the inpatient substance abuse treatment program (SATP). To decrease his cocaine craving, Mr. A was given desipramine in a daily divided dose of 150 mg. Desipramine did initially decrease the intensity of the craving (Gawin et al., 1989). However it did not decrease his behavior of constantly searching for crack cocaine on carpeted floors, the furniture, and in the bathrooms. After being on desipramine for 1 week, Mr. A developed urinary hesitancy (Pollack & Rosenbaum, 1987), and he asked that it be discontinued. Because he complained of persistent insomnia, he was given trazodone 50 mg at bedtime. This improved his sleep (Montgomery, Oswald, Morgan, & Adam, 1983), and he also noticed that it decreased his anxious feelings (Liebowitz, & E1-Mallakh, 1989) during the day. His dose was gradually increased up to 200 mg daily given at bedtime. Two weeks following the beginning of treatment with trazodone, the compulsive foraging behavior of searching for crack cocaine subsided. Mr. A was discharged from the SATP to the outpatient rehabilitation program. During a follow-up period of 3 months, foraging behavior did not re-emerge. The patient was compliant with taking 200 mg of trazodone daily, and he continued to abstain from crack cocaine. Patient B
A 27-year-old White female presented to the psychiatry crisis center complaining of inability to control her urges "of constantly checking her clothes for pieces of crack cocaine." Ms. B had never abused any alcohol or other drugs and did not have any prior medical or psychiatric illnesses. Ms. B smoked crack for the first time 3 months ago and at the time of presentation had been smoking up to 2 grams o f crack daily. For the 4 weeks prior to admission, she began repeatedly checking her clothes, shoes, pockets, and socks hoping to find pieces of crack cocaine. One week prior to admission, she developed severe cravings and as a result would leave her desk at work approximately every half hour and sneak to the restroom to smoke crack. If she could not smoke the crack, she would engage in the ritualistic behavior of constantly checking her clothes for pieces o f crack cocaine. Ms. B took a leave of absence from her job and became increasingly fearful of leaving her house due to the inability to control the intense urges o f constantly checking her clothes. Although she had never had any episode of
H . R . K h o u z a m et al.
indecent behaviors, she worried about being arrested if she took her clothes off in public to check for pieces of crack. Ms. B was referred from the crisis center and admitted to the SATP. Physical examination and laboratory tests including electrolytes, CBC, UA, TFT, CXR, and ECG were normal. Urine drug screen was positive for cocaine metabolites but negative for other drugs of abuse. Treatment began with bromocriptine 0.625 mg q.i.d. (Giannini & Billet, 1987). However, Ms. B continued to experience cravings for the crack, so she was started on desipramine (Gawin et al., 1989) 25 mg daily, which was gradually increased to 150 mg divided dose daily over a 14-day period. Desipramine did alleviate the severe cravings, but the compulsive foraging behavior of constantly checking the clothes for crack intensified. When desipramine was tapered down and finally discontinued, Ms. B experienced persistent difficulty with falling asleep. Trazodone was initiated at a dose of 50 mg at bedtime (Montgomery et al., 1983). Over the following 5 days, trazodone was gradually increased, and finally, at a bedtime dose of 200 mg, the insomnia subsided. Ms. B did not report any side effects due to the trazodone and was surprised to notice that after being on the 200-mg dose for 10 days her urges to constantly check her clothes for pieces of crack subsided. Ms. B requested to be maintained on trazodone at the same 200-mg daily bedtime dose. This was done, and 6 months following her discharge from the SATP, the patient continued to abstain from abusing crack and did not relapse into the compulsive foraging behavior. Patient C
A 35-year-old African-American male with documented history of hypertension was brought to the ER by his wife following an episode of severe headache that started early on that morning. Mr. C's past history included noncompliance with treatment for hypertension and a pattern of daily abuse of alcohol and crack cocaine over the last 9 months. The patient's blood pressure upon arrival at the ER was 209/119 mmHg. His blood pressure was treated, and he was admitted to the SATP for cocaine abuse treatment. Physical examination, electrolytes, CBC, UA, TFT, CXR, and ECG were all normal. During his first week of rehabilitation treatment, Mr. C did not report cravings for cocaine. With the beginning of the second week, the nursing staff observed Mr. C constantly checking the window sill in his room. When he was asked about the purpose of his checking, he acknowledged that he was searching for pieces of crack cocaine. During a treatment team evaluation meeting, Mr. C admitted being totally helpless toward stopping his behavior of checking the window sill in search for pieces of crack cocaine despite knowing that his search was in vain. Mr. C was started on desipramine (Ga-
Treatment of Compulsive Behavior With Trazodone
win et al., 1989), 25 mg a day, which was gradually increased to 150 mg divided daily dose over a 15-day period. Mr. C developed an agitated response to desipramine (Roehrich & Gold, 1991), so it was discontinued and trazodone initiated at a dose of 50 mg three times daily (Louie, Lannon, & Ketler, 1989). Mr. C did not report any side effects of trazodone. Three weeks after initiation of trazodone treatment, the foraging behavior of constantly checking the window sills for pieces of crack cocaine subsided. Mr. C was discharged from the SATP and was followed by the outpatient rehabilitation program. He was maintained on trazodone 150 mg daily in divided doses. During a 3-month follow-up period, he remained compliant with the trazodone treatment and did not relapse into abusing crack cocaine. His foraging behavior has not reemerged, and he has remained abstinent from alcohol and compliant with medical follow-up for hypertension. Mr. C also became spiritually involved and did report the following verse: "I am free from the power of cocaine and God's benefits to me include holiness and everlasting life" (paraphrasing Romans, 6:22) as an important factor in his recovery.
DISCUSSION Cocaine is usually used in binges of a few hours to a week. When a patient stops, or "crashes," craving may persist for a few hours, but for the next 3-5 days, fatigue, depression, increased sleep, and increased appetite may occur. This stage has been called Phase 1 (Gawin et al., 1989) and has low risk of relapse. Over the next 1-10 weeks, the patient progresses from feeling euthymic with mild cocaine craving to a state of high craving with anhedonia, anergia, and dysphoria. If the patient gets through this stage, called Phase 2, then craving becomes only occasional although it can be triggered by conditioned cues like objects, places, or environmental stimuli similar to the scenes where cocaine was used. Several pharmacotherapies have been tried in Phase l, including bromocriptine (Giannini & Billet, 1987) and amantadine (Tennant & Sagherian, 1987), but with little obvious efficacy in controlled trials (Michels & Marzuk, 1993). Desipramine has been shown to be somewhat effective in reducing dysphoria and craving in Phase 2 (60O7o abstinence in desipramine patients vs. 17°7oabstinence on placebo; Gawin et al., 1989). Other antidepressants might do as well, but desipramine was chosen because of its predominant norepinephrine (NE) effect and its relatively good side-effect profile (Schatzberg & Cole, 1991). For the more prolonged Phase 3, which begins after 6 weeks of abstinence and can last for months or years, controlled trials have not been performed (Michels & Marzuk, 1993).
87
The three patients described here did not tolerate desipramine side effects. Trazodone treatment was initiated for symptomatic relief of insomnia (in Patients A and B) and agitation (in Patient C). After the trazodone was initiated, a dramatic resolution of the foraging behavior was observed. However, as this was not a controlled study, we cannot determine if this resolution was just incidental due to the passage of time or the result of trazodone-specific pharmacological actions. The pharmacology of the antidepressant trazodone is complex and in some ways resembles that of the tricyclic antidepressants, the benzodiazepines, and the phenothiazines. However, the overall pharmacologic profile of trazodone differs from each of these classes of medications. The precise mechanism of action of trazodone is unclear, but it has been shown to selectively block the reuptake of serotonin 5-hydroxytryptamine at the presynaptic neuronal membrane. Thus, the central nervous system (CNS) effects of serotonin are potentiated. Trazodone does not appear to influence the reuptake of dopamine (DA) or NE within the CNS. The sedative effect of trazodone is thought to result from central alpha 1-adrenergic blocking activity. Although the exact mechanism of action has not been determined, trazodone also possesses significant anxiolytic properties (Liebowitz & EI-Mallakh, 1989). In these three patients, the development of the compulsive foraging behavior did not seem to be a consequence of intense craving for crack cocaine but a possible drug-induced type of compulsion (Rosse et al., 1993). Abnormality of crack serotonergic neural transmission has been implicated in obsessive-compulsive disorder (OCD) and cocaine abuse (Rosse et al., 1993). Because these three patients did not have a prior history of OCD, one could speculate that cocaine-induced foraging behavior might represent a drug-induced type of compulsive disorder. Serotonergic receptor supersensitivity could be a neurochemical substrate for postcocaine compulsive behaviors and consequently contribute to relapse and inability to maintain abstinence. Although obsessive compulsive symptomatology is associated with adverse mood states (Farid, 1986), none of the three patients had an underlying mood disorder prior to abusing crack cocaine. It appears that if, in fact, trazodone was contributing to the remission, this was not due to its antidepressant effects but rather a result of its antiobsessional properties (Hermesh, Aizenberg, & Munitz, 1990). In conclusion, these three cases support the concept that serotonin may be involved in mediating a crackcocaine-induced compulsive foraging behavior. Trazodone as a selective serotonin reuptake inhibitor (SSRI) as well as other SSRI such as fluoxetine, sertraline, paroxetine, and fluvoxamine could be efficacious pharmacotherapies for the treatment of the compulsive foraging behavior. However, we feel these cases
88
H.R. Khouzam et al.
represent interesting observations only, and this hypothesis needs further testing in well-designed placebocontrolled randomized trials. REFERENCES Brady, K.T., Lydiard, R.B., Malcolm, R., & Ballenger, J.C. (1991). Cocaine-induced psychosis. Journal of Clinical Psychiatry, 52, 509-512. Ellinwood, E.H., Jr., Sudilovsky, A., & Nelson, L.M. (1973). Evolving behavior in the clinical and experimental amphetamine (model) psychosis. American Journal of Psychiatry, 130, 10881093. Farid, B.T. (1986). Obsessional symptomatology and adverse mood states. British Journal of Psychiatry, 149, 108-112. Gawin, F.H., Kleber, H.D., Byck, R., Rounsaville, B.J., Kosten, T.R., Jatlow, P.I., & Morgan, C. (1989). Desipramine facilitation of initial cocaine abstinence. Archives of General Psychiatry, 46, 117-121. Giannini, A.J., & Billet, T.S. (1987). Bromocriptine-desipramine protocol in cocaine detoxification. Journal of Clinical Pharmacology, 27, 549-556. Hermesh, H., Aizenberg, D., & Munitz, H. (1990). Trazodone treatment in clomipramine-resistant obsessive compulsive disorder. Clinical Neuropharmacology, 13, 322-328. Liebowitz, N.R., & EI-Mallakh, R.S. (1989). Trazodone for the treatment of anxiety symptoms in substance abusers. Journal of Clinical Psychopharmacology, 9, 449-450.
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