CASE REPORT
Intravenous Administration and Abuse of Bupropion: A Case Report and a Review of the Literature Kirsten Oppek, MD, Gabriele Koller, MD, Andreas Zwergal, MD, and Oliver Pogarell, MD
Introduction: Bupropion is an effective and well-tolerated secondgeneration antidepressant generally assumed to be without abuse potential. In the past years, several case reports about the recreational use of bupropion, mainly via nasal insufflation, have been published. Last year, a first case of intravenous bupropion dependence was reported. Case presentation: We present another case of intravenous administration of and dependence on bupropion in a 29-year-old woman with a history of polysubstance dependence, who consumed an extremely high daily dose of about 2400 mg of bupropion together with a daily oral dose of 2400 to 3600 mg of pregabalin. Discussion: The possible impact of bupropion on subjects with a history of polysubstance dependence is discussed; physicians should be careful when prescribing bupropion in these cases. Key Words: dependence on bupropion, intravenous administration of bupropion, polysubstance dependence (J Addict Med 2014;8: 290–293)
B
upropion is an atypical antidepressant approved for the treatment of major depressive disorders and as a smoking cessation aid. In contrast to other widely used antidepressants, its mechanism of action is a reuptake inhibition of dopamine and norepinephrine (Moreira, 2011). Furthermore, bupropion is a synthetic cathinone sharing some structural properties with psychostimulants (Dwoskin et al., 2006). This structural similarity has given rise to the discussion about potential stimulant effects, and the abuse potential of bupropion is a point of controversy.
CASE PRESENTATION Current Complaint A 29-year-old woman with a history of polysubstance dependence was admitted to our hospital for withdrawal from intravenous bupropion and oral pregabalin administration. From the Department of Psychiatry and Psychotherapy (KO, GK, OP) and the Department of Neurology (AZ), Ludwig-Maximilians-University Munich, Munich, Germany. Received for publication January 11, 2014; accepted March 23, 2014. The authors declare no conflicts of interest. Patient consent was obtained to write this case report. Send correspondence and reprint requests to Kirsten Oppek, MD, Department of Psychiatry and Psychotherapy, Ludwig-MaximiliansUniversity Munich, Nussbaumstraße 7, 80336 Munich, Germany. E-mail: [email protected]. C 2014 American Society of Addiction Medicine Copyright ISSN: 1932-0620/14/0804-0290 DOI: 10.1097/ADM.0000000000000044
290
Initially, bupropion was prescribed for the treatment of her depressive disorder and to avoid gaining weight as an adverse effect. Before beginning intravenous abuse, she had been taking an oral dose of 300 mg (sustained release) for about 3 to 4 months. Having increased the oral daily dose to 450 mg/d, she mentioned a transient feeling comparable with the consumption of amphetamines. Subsequently, she started intravenous administration. By pulling off the coating and dissolving the tablet in hot water, she created a liquid for injection. After injection, she experienced a short feeling similar to the consumption of cocaine of poor quality. At the time of hospital admission, she had been administering bupropion intravenously for about 11/2 months on a daily basis. The current daily dose of bupropion was approximately 2400 mg (8 × 300 mg tablets). Regarding physical withdrawal symptoms, she reported periods of psychomotor agitation occurring within hours after consumption. Furthermore, she observed a very distinct craving for bupropion, so that she “just could not stop injecting.” She also reported a decreased urge to smoke. In addition, she had been abusing pregabalin for about 11/2 years, currently at a dose of 2400 to 3600 mg/d. She initially took 300 mg daily, which induced a feeling similar to drunkenness. She increased the dose slowly, especially during administration of high doses of bupropion, hoping to prevent seizures. Pregabalin was acquired off the streets, whereas her physician generously prescribed bupropion for months in advance. However, her physician became suspicious and refused to prescribe bupropion any longer, which contributed to the patient’s decision to attend a detoxification unit for withdrawal.
Medical History At the age of 14 years, our patient insufflated heroin out of interest. At approximately 17 years of age, she administered heroin intravenously and began experimenting with other substances including cocaine, amphetamine, and ecstasy. At the age of 20 years, she started consuming benzodiazepines. She had been on an opiate maintenance therapy (up to 80 mg of methadone or equivalent) for several periods, during which there had also been an irregular abuse of alcohol. The last withdrawal from substances (heroin, fentanyl, alcohol, and benzodiazepines) took place in 2011. The last consumption of illegal substances (heroin) was approximately a month before admission. Apart from polysubstance dependence, she suffered from a depressive illness. Furthermore, there was evidence suggesting a body image disturbance without meeting the diagnostic criteria for an eating disorder. Several generalized J Addict Med r Volume 8, Number 4, July/August 2014
Copyright © 2014 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited.
J Addict Med r Volume 8, Number 4, July/August 2014
seizures occurred in the past, most of them directly associated with substance withdrawal (eg, benzodiazepines). The last seizure was reported about a month before admission after intravenous administration of a high dose of bupropion. Her medical history contained a positive serology for hepatitis C. She was treated for septicemia related to intravenous drug abuse about 7 years ago. The patient had surgery for varicose veins about a month before admission. Her current medication consisted of rivaroxaban, which was administered because of suspected inguinal thrombosis. There was no opiate maintenance therapy.
Intravenous Administration and Abuse of Bupropion
was discontinued. To prevent seizures, levetiracetam (daily dose of 1000 mg) was initiated. Pregabalin was initially administered at a daily dose of 600 mg. The reduction of pregabalin began 11 days after admission and withdrawal lasted for 8 days. Withdrawal was tolerated well without any withdrawal symptoms. There were neither seizures nor periods of hemodynamic instability. After about 3 weeks, the values of transaminases were back to normal. For further treatment, the patient planned to attend outpatient facilities for subjects with substance abuse.
Clinical Findings In the mental state examination, there were formal thought disorders in terms of increased distractibility and incoherence and disorders of thought content in terms of emerging delusional ideas (eg, people in the streets might think of her in a bad way), which our patient herself related to the abuse of bupropion. She stated that she became “a little bit more paranoid” and that she was “just managing to rationalize these thoughts away.” However, there were also brief periods beyond reality with clear delusional content. Furthermore, there were an increased lability of mood, disturbed sleep, and increased energy. Urine drug screening was negative. Blood levels of bupropion and hydroxy-bupropion were markedly elevated (Table 1). There were electroencephalogram–proven sporadic generalized singular spike-wave complexes. The electrocardiogram did not show any pathological features. A cranial magnetic resonance imaging scan revealed no detectable abnormalities except a small pineal cyst without compression to surrounding structures. On admission, our patient demonstrated moderate withdrawal symptoms (psychomotor agitation, restless legs, and lability of mood), which decreased continuously and lasted for about 7 days. Muscle pain in her legs was first reported about 35 hours after admission and lasted for about 10 days. Ravenous appetite developed slowly during the first 3 days and decreased continuously.
Management and Outcome To support withdrawal from bupropion, our patient received 25 mg of quetiapine 4 times a day for 7 days. Her ravenous appetite could have been associated with the administration of quetiapine. After stabilization of mood, quetiapine
TABLE 1. Extract From Laboratory Values (Only Elevated Values on Admission Are Shown) Parameter AST ALT LDH CK Bupropion level Hydroxy-bupropion level
Measured Value
Reference
87 U/L 134 U/L 482 U/L 645 U/L 226 μg/L 3330 μg/L
Intravenous Administration and Abuse of Bupropion: A Case Report and a Review of the Literature Kirsten Oppek, MD, Gabriele Koller, MD, Andreas Zwergal, MD, and Oliver Pogarell, MD
Introduction: Bupropion is an effective and well-tolerated secondgeneration antidepressant generally assumed to be without abuse potential. In the past years, several case reports about the recreational use of bupropion, mainly via nasal insufflation, have been published. Last year, a first case of intravenous bupropion dependence was reported. Case presentation: We present another case of intravenous administration of and dependence on bupropion in a 29-year-old woman with a history of polysubstance dependence, who consumed an extremely high daily dose of about 2400 mg of bupropion together with a daily oral dose of 2400 to 3600 mg of pregabalin. Discussion: The possible impact of bupropion on subjects with a history of polysubstance dependence is discussed; physicians should be careful when prescribing bupropion in these cases. Key Words: dependence on bupropion, intravenous administration of bupropion, polysubstance dependence (J Addict Med 2014;8: 290–293)
B
upropion is an atypical antidepressant approved for the treatment of major depressive disorders and as a smoking cessation aid. In contrast to other widely used antidepressants, its mechanism of action is a reuptake inhibition of dopamine and norepinephrine (Moreira, 2011). Furthermore, bupropion is a synthetic cathinone sharing some structural properties with psychostimulants (Dwoskin et al., 2006). This structural similarity has given rise to the discussion about potential stimulant effects, and the abuse potential of bupropion is a point of controversy.
CASE PRESENTATION Current Complaint A 29-year-old woman with a history of polysubstance dependence was admitted to our hospital for withdrawal from intravenous bupropion and oral pregabalin administration. From the Department of Psychiatry and Psychotherapy (KO, GK, OP) and the Department of Neurology (AZ), Ludwig-Maximilians-University Munich, Munich, Germany. Received for publication January 11, 2014; accepted March 23, 2014. The authors declare no conflicts of interest. Patient consent was obtained to write this case report. Send correspondence and reprint requests to Kirsten Oppek, MD, Department of Psychiatry and Psychotherapy, Ludwig-MaximiliansUniversity Munich, Nussbaumstraße 7, 80336 Munich, Germany. E-mail: [email protected]. C 2014 American Society of Addiction Medicine Copyright ISSN: 1932-0620/14/0804-0290 DOI: 10.1097/ADM.0000000000000044
290
Initially, bupropion was prescribed for the treatment of her depressive disorder and to avoid gaining weight as an adverse effect. Before beginning intravenous abuse, she had been taking an oral dose of 300 mg (sustained release) for about 3 to 4 months. Having increased the oral daily dose to 450 mg/d, she mentioned a transient feeling comparable with the consumption of amphetamines. Subsequently, she started intravenous administration. By pulling off the coating and dissolving the tablet in hot water, she created a liquid for injection. After injection, she experienced a short feeling similar to the consumption of cocaine of poor quality. At the time of hospital admission, she had been administering bupropion intravenously for about 11/2 months on a daily basis. The current daily dose of bupropion was approximately 2400 mg (8 × 300 mg tablets). Regarding physical withdrawal symptoms, she reported periods of psychomotor agitation occurring within hours after consumption. Furthermore, she observed a very distinct craving for bupropion, so that she “just could not stop injecting.” She also reported a decreased urge to smoke. In addition, she had been abusing pregabalin for about 11/2 years, currently at a dose of 2400 to 3600 mg/d. She initially took 300 mg daily, which induced a feeling similar to drunkenness. She increased the dose slowly, especially during administration of high doses of bupropion, hoping to prevent seizures. Pregabalin was acquired off the streets, whereas her physician generously prescribed bupropion for months in advance. However, her physician became suspicious and refused to prescribe bupropion any longer, which contributed to the patient’s decision to attend a detoxification unit for withdrawal.
Medical History At the age of 14 years, our patient insufflated heroin out of interest. At approximately 17 years of age, she administered heroin intravenously and began experimenting with other substances including cocaine, amphetamine, and ecstasy. At the age of 20 years, she started consuming benzodiazepines. She had been on an opiate maintenance therapy (up to 80 mg of methadone or equivalent) for several periods, during which there had also been an irregular abuse of alcohol. The last withdrawal from substances (heroin, fentanyl, alcohol, and benzodiazepines) took place in 2011. The last consumption of illegal substances (heroin) was approximately a month before admission. Apart from polysubstance dependence, she suffered from a depressive illness. Furthermore, there was evidence suggesting a body image disturbance without meeting the diagnostic criteria for an eating disorder. Several generalized J Addict Med r Volume 8, Number 4, July/August 2014
Copyright © 2014 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited.
J Addict Med r Volume 8, Number 4, July/August 2014
seizures occurred in the past, most of them directly associated with substance withdrawal (eg, benzodiazepines). The last seizure was reported about a month before admission after intravenous administration of a high dose of bupropion. Her medical history contained a positive serology for hepatitis C. She was treated for septicemia related to intravenous drug abuse about 7 years ago. The patient had surgery for varicose veins about a month before admission. Her current medication consisted of rivaroxaban, which was administered because of suspected inguinal thrombosis. There was no opiate maintenance therapy.
Intravenous Administration and Abuse of Bupropion
was discontinued. To prevent seizures, levetiracetam (daily dose of 1000 mg) was initiated. Pregabalin was initially administered at a daily dose of 600 mg. The reduction of pregabalin began 11 days after admission and withdrawal lasted for 8 days. Withdrawal was tolerated well without any withdrawal symptoms. There were neither seizures nor periods of hemodynamic instability. After about 3 weeks, the values of transaminases were back to normal. For further treatment, the patient planned to attend outpatient facilities for subjects with substance abuse.
Clinical Findings In the mental state examination, there were formal thought disorders in terms of increased distractibility and incoherence and disorders of thought content in terms of emerging delusional ideas (eg, people in the streets might think of her in a bad way), which our patient herself related to the abuse of bupropion. She stated that she became “a little bit more paranoid” and that she was “just managing to rationalize these thoughts away.” However, there were also brief periods beyond reality with clear delusional content. Furthermore, there were an increased lability of mood, disturbed sleep, and increased energy. Urine drug screening was negative. Blood levels of bupropion and hydroxy-bupropion were markedly elevated (Table 1). There were electroencephalogram–proven sporadic generalized singular spike-wave complexes. The electrocardiogram did not show any pathological features. A cranial magnetic resonance imaging scan revealed no detectable abnormalities except a small pineal cyst without compression to surrounding structures. On admission, our patient demonstrated moderate withdrawal symptoms (psychomotor agitation, restless legs, and lability of mood), which decreased continuously and lasted for about 7 days. Muscle pain in her legs was first reported about 35 hours after admission and lasted for about 10 days. Ravenous appetite developed slowly during the first 3 days and decreased continuously.
Management and Outcome To support withdrawal from bupropion, our patient received 25 mg of quetiapine 4 times a day for 7 days. Her ravenous appetite could have been associated with the administration of quetiapine. After stabilization of mood, quetiapine
TABLE 1. Extract From Laboratory Values (Only Elevated Values on Admission Are Shown) Parameter AST ALT LDH CK Bupropion level Hydroxy-bupropion level
Measured Value
Reference
87 U/L 134 U/L 482 U/L 645 U/L 226 μg/L 3330 μg/L
