626345
research-article2015
TPP0010.1177/2045125315626345Therapeutic Advances in PsychopharmacologyR. N. Yuksel et al.
Therapeutic Advances in Psychopharmacology
Review
Cabergoline-induced manic episode: case report Rabia Nazik Yüksel, Zeynep Elyas Kaya, Nesrin Dilbaz and Merve Cingi Yirün
Ther Adv Psychopharmacol 2016, Vol. 6(3) 229–231 DOI: 10.1177/ 2045125315626345 © The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Abstract: Cabergoline is an orally administered synthetic dopamine agonist that is used for the treatment of hyperprolactinemia, Parkinson’s disease and antipsychotic-induced prolactin elevation. One of the main characteristics of cabergoline is its long duration of effect. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral dose. The prolonged elimination half-life offers an advantage of once-daily dosing, but it might be a handicap in terms of washout of adverse effects such as psychosis. Cabergoline has been associated with adverse reactions consistent with other dopaminergic agonists including cardiovascular, gastrointestinal and neuropsychiatric effects. It is known that dopaminergic treatment is a remarkable risk factor for psychosis. A number of reports implicate dopamine agonists in the development of psychosis, but there is no knowledge in the literature of dopamine agonistinduced mania. In this case, we report the first manic episode occurring after cabergoline use for hyperprolactinemia treatment. In susceptible individuals, cabergoline can cause manic episodes and cabergoline should be used more carefully considering the risk–benefit ratio.
Keywords: Cabergoline, Bipolar Disorder, Mania, Dopamine agonists, dostinex, drug-induced mania, Affective Disorders Introduction Cabergoline (dostinex) is a synthetic tetracyclic ergolin derivative that has a selective agonistic effect on D2 receptors. It does not have a significant effect on D1 receptors. Just like the other ergotamines, it also has nondopaminergic (noradrenergic and seratonergic) effects [Fariello, 1998]. Cabergoline suppresses prolactin secretion and causes nausea, vomiting, and orthostatic hypotension. Cabergoline is used for the treatment of hyperprolactinemia and Parkinsonism in many countries. It is administered at a rate of 0.25–3.5 mg per week in hyperprolactinemia, while much larger doses, in the order of 2–6 mg per day, are used in Parkinsonism. On the other hand, some studies report its benefits in the treatment of drug-related hyperprolactinemia [Cavallaro et al. 2004]. One of the most important features of cabergoline is its long-lasting effect after oral administration due to its long elimination half-life of nearly 65 hours. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral
dose [Movement Disorder Society, 2002]. Like other dopaminergic agonists, cabergoline has gastrointestinal, cardiovascular, and neuropsychiatric side effects. There is no significant evidence demonstrating that cabergoline has a safer profile than other ergotamine derivatives like bromocriptine. Although cabergoline has the advantage of a single-day dosage, the disadvantages of this treatment regimen have not been fully understood yet. For example, this long-lasting action may cause difficulties managing some side effects like psychosis. It is already known that dopaminergic treatment is an important risk factor for psychosis. Some studies have reported that dopamine agonists induce psychosis [Arnold et al. 2005; Boyd, 1995; Perea et al. 2006; Pezzoli et al. 1994, 1995; Rascol, 1999; Schrag et al. 1998; Storch et al. 2005; Chang et al. 2008]. Also, two case presentations report that cabergoline induces exacerbation of psychosis in schizophrenic patients. However, the literature includes no data suggesting that dopaminergic agonists induce mania. This case report presents an analysis of the association between a manic episode and cabergoline.
Correspondence to: Rabia Nazik Yüksel, MD Ankara Numune Training and Research Hospital, Talatpasa Bulvari, No: 5, D Blok, 1. Kat Psikiyatri, Ankara, Turkey [email protected] Zeynep Elyas Kaya, MD Elazig Egitim ve Arastirma Hastanesi, Turkey Nesrin Dilbaz, MD Üsküdar Üniversitesi, Turkey Merve Cingi Yirün, MD Ankara Numune Training and Research Hospital, Turkey
http://tpp.sagepub.com 229
Therapeutic Advances in Psychopharmacology 6(3) Case presentation This case report focuses on a 26-year-old woman: a married high-school graduate, housewife, and mother of one, who gave birth 15 months ago. A month ago, she was diagnosed with polycystic ovarian syndrome and subsequently treated with a levonorgestrel-containing intrauterine device. Cabergoline was started at 0.5 mg once per day to stop lactating. Two days after the first dose of cabergoline, the patient complained of irritation, insomnia, and a short temper. She locked her child and herself into a room and then removed everything that might hurt somebody at home. She worried that her child was going to be harmed by a spell that someone had cast on their house. She started to talk to herself and then began arguing with her husband. This led to her later throwing a lot of his belongings away and kicking him out of the house. She also began listening to music at high volume, laughing loudly, and spending much more money than usual. Her religious preoccupations increased. She was not as healthy as usual during that two-week period. In the final week, she even began to neglect her child and her home. She began to think she had some special power. She was laughing loudly, having difficulty sleeping, talking too much, and harming her child in the last few days. The patient was admitted to our emergency room and hospitalized in a psychiatry clinic with the prediagnosis of manic episode with psychotic features. Her mental status examination revealed that the content of her thoughts revealed grandiose and paranoid delusions. She was irritable; her mood was labile and grandiose; and she had a euphoric facial expression. Reality testing was partially impaired. Her judgment and her ability to abstract were also impaired. She exhibited rapid associations, pressured speech, and a flight of ideas. She demonstrated psychomotor hyperactivity and her Young Mania Rating Scale score was calculated as 39. There were no abnormalities in her physical examination and laboratory results. Her cranial MRI was normal. Her dostinex treatment was stopped, and a new treatment was initiated of 20 mg/day of olanzapine, and 600 mg/day of carbamazepine was added as a mood stabilizer. At the end of the second week, the carbamazepine treatment was stopped because of carbamazepineinduced hyponatremia, and a 900 mg/day lithium treatment was started. The psychomotor hyperactivity, irritability, and grandiosity of the patient persisted, and her Young Mania Rating Scale score was 19. Her daily olanzapine dose was increased from 20 to 30 mg. At the end of third
week, her Young Mania Rating Scale score was down to 6. An examination of her mental status showed that her mood was euthymic, her grandiose thoughts had disappeared, and her psychomotor activity was normal. Her elevated mood was significantly improved, as her adaptation to clinical conditions and medications was successful. She was discharged with a treatment regimen of 900 mg/day of lithium and 30 mg/day of olanzapine. During her three weeks of clinical observation, her Clinical Global Impressions-Severity (CGI-S) scores were 5, 3, and 1 for the second, third, and fourth weeks, respectively, and her Clinical Global Impressions- Improvement (CGII) scores were 3, 2, and 1 for the second, third, and fourth weeks, respectively. Discussion Goal-directed actions, antidepressants, distortion of circadian rhythm, seasonal changes of especially spring and autumn, stressful life events, and increased emotional expression are previously shown precipitating factors for hypomanic or manic episodes in susceptible individuals [Proudfoot et al. 2011]. Although it has previously been shown that dopamine agonists have aggravating effects on psychosis in schizophrenic patients [Factor et al. 1995], there is not much information about their inducing effects on mania. This case reviewed a manic episode with psychotic features that emerged after use of cabergoline, a dopaminergic agonist with a half-life of 65 hours. Its effect can last nearly 21 days after usage of a single dose. Therefore, managing its side effects is difficult. In this case, the patient’s symptoms started after two days of a single dose of 0.5 mg cabergoline. The timing of the symptoms and the course of the disorder led us to conclude that this manic episode was induced by cabergoline use. Some studies have been reported that it is safer to use cabergoline than bromocriptine in terms of inducing psychosis. [Di Salle et al. 1983] Therefore cabergoline is more commonly preferred in treatment of hyperprolactinemia. However, this situation is probably due to insufficient number of studies about cabergoline’s neuropsychiatric side effects. Although cabergoline is highly effective in hyperprolactinemia treatment, it may induce hypomanic/manic episodes in susceptible individuals, such as in this case. Risk–benefit ratio should be analyzed with prospective controlled studies in
230 http://tpp.sagepub.com
RN Yuksel, ZE Kaya et al. future and cabergoline must be used carefully in susceptible individuals as much as other dopaminergic agonists Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
Fariello, R. (1998) Pharmacodynamic and pharmacokinetic features of cabergoline. Rationale for use in Parkinson’s disease. Drugs 55: 10–16. Movement Disorder Society (2002) DA agonists-ergot derivatives: cabergoline. Mov Disord 17: S68–S71. Perea, E., Robbins, B. and Hutto, B. (2006) Psychosis related to ropinirole. Am J Psychiat 163: 547–548.
Conflict of interest statement The authors declare that there is no conflict of interest.
Pezzoli, G., Martignoni, E., Pacchetti, C., Angeleri, V., Lamberti, P., Muratorio, A. et al. (1994) Pergolide compared with bromocriptine in Parkinson’s disease: a multicenter, crossover, controlled study. Mov Disord 9: 431–436.
References
Pezzoli, G., Martignoni, E., Pacchetti, C., Angeleri, V., Lamberti, P., Muratorio, A. et al. (1995) A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson’s disease. Neurology 45: S22–S27.
Arnold, G., Gasser, T., Storch, A., Lipp, A., Kupsch, A., Hundemer, H. et al. (2005) High doses of pergolide improve clinical globalimpression in advanced Parkinson’s disease: – a preliminary open label study. Arch Gerontol Geriatr 41: 239–253. Boyd, A. (1995) Bromocriptine and psychosis: a literature review. Psychiatr Quart 66: 87–95. Cavallaro, R., Cocchi, F., Angelone, S., Lattuada, E. and Smeraldi, E. (2004) Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study. J Clin Psychiatr 65: 187–190. Chang, S., Chen, C. and Lu, M. (2008) Cabergolineinduced psychotic exacerbation in schizophrenic patients. Gen Hosp Psychiatr 30: 378–380. Di Salle, E., Ornati, G., Giudici, D. and Britanico, G. (1983) Prolactin-lowering effect of a new ergoline derivative, FCE 21336, in the rat: a comparison with bromocriptine. Acta Endocrinol 103: 265. Factor, S., Molho, E., Podskalny, G. and Brown, D. (1995) Parkinson’s disease: drug-induced psychiatric states. Adv Neurol 65: 115–138.
Proudfoot, J., Doran, J., Manicavasagar, V. and Parker, G. (2011) The precipitants of manic/ hypomanic episodes in the context of bipolar disorder: A review. J Affect Disord 133: 381–387. Rascol, O. (1999) Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson’s disease? J Neur TR S 55: 33–45. Schrag, A., Brooks, D., Brunt, E., Fuell, D., Korczyn, A., Poewe, W. et al. (1998) The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson’s disease. Clin Neuropharmacol 21: 169–175. Storch, A., Trenkwalder, C., Oehlwein, C., Winkelmann, J., Polzer, U., Hundemer, H. et al. (2005) High-dose treatment with pergolide in Parkinson’s disease patients with motor fluctuations and dyskinesias. Parkinsonism Relat D 11: 393–398.
Visit SAGE journals online http://tpp.sagepub.com
SAGE journals
http://tpp.sagepub.com 231
research-article2015
TPP0010.1177/2045125315626345Therapeutic Advances in PsychopharmacologyR. N. Yuksel et al.
Therapeutic Advances in Psychopharmacology
Review
Cabergoline-induced manic episode: case report Rabia Nazik Yüksel, Zeynep Elyas Kaya, Nesrin Dilbaz and Merve Cingi Yirün
Ther Adv Psychopharmacol 2016, Vol. 6(3) 229–231 DOI: 10.1177/ 2045125315626345 © The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Abstract: Cabergoline is an orally administered synthetic dopamine agonist that is used for the treatment of hyperprolactinemia, Parkinson’s disease and antipsychotic-induced prolactin elevation. One of the main characteristics of cabergoline is its long duration of effect. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral dose. The prolonged elimination half-life offers an advantage of once-daily dosing, but it might be a handicap in terms of washout of adverse effects such as psychosis. Cabergoline has been associated with adverse reactions consistent with other dopaminergic agonists including cardiovascular, gastrointestinal and neuropsychiatric effects. It is known that dopaminergic treatment is a remarkable risk factor for psychosis. A number of reports implicate dopamine agonists in the development of psychosis, but there is no knowledge in the literature of dopamine agonistinduced mania. In this case, we report the first manic episode occurring after cabergoline use for hyperprolactinemia treatment. In susceptible individuals, cabergoline can cause manic episodes and cabergoline should be used more carefully considering the risk–benefit ratio.
Keywords: Cabergoline, Bipolar Disorder, Mania, Dopamine agonists, dostinex, drug-induced mania, Affective Disorders Introduction Cabergoline (dostinex) is a synthetic tetracyclic ergolin derivative that has a selective agonistic effect on D2 receptors. It does not have a significant effect on D1 receptors. Just like the other ergotamines, it also has nondopaminergic (noradrenergic and seratonergic) effects [Fariello, 1998]. Cabergoline suppresses prolactin secretion and causes nausea, vomiting, and orthostatic hypotension. Cabergoline is used for the treatment of hyperprolactinemia and Parkinsonism in many countries. It is administered at a rate of 0.25–3.5 mg per week in hyperprolactinemia, while much larger doses, in the order of 2–6 mg per day, are used in Parkinsonism. On the other hand, some studies report its benefits in the treatment of drug-related hyperprolactinemia [Cavallaro et al. 2004]. One of the most important features of cabergoline is its long-lasting effect after oral administration due to its long elimination half-life of nearly 65 hours. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral
dose [Movement Disorder Society, 2002]. Like other dopaminergic agonists, cabergoline has gastrointestinal, cardiovascular, and neuropsychiatric side effects. There is no significant evidence demonstrating that cabergoline has a safer profile than other ergotamine derivatives like bromocriptine. Although cabergoline has the advantage of a single-day dosage, the disadvantages of this treatment regimen have not been fully understood yet. For example, this long-lasting action may cause difficulties managing some side effects like psychosis. It is already known that dopaminergic treatment is an important risk factor for psychosis. Some studies have reported that dopamine agonists induce psychosis [Arnold et al. 2005; Boyd, 1995; Perea et al. 2006; Pezzoli et al. 1994, 1995; Rascol, 1999; Schrag et al. 1998; Storch et al. 2005; Chang et al. 2008]. Also, two case presentations report that cabergoline induces exacerbation of psychosis in schizophrenic patients. However, the literature includes no data suggesting that dopaminergic agonists induce mania. This case report presents an analysis of the association between a manic episode and cabergoline.
Correspondence to: Rabia Nazik Yüksel, MD Ankara Numune Training and Research Hospital, Talatpasa Bulvari, No: 5, D Blok, 1. Kat Psikiyatri, Ankara, Turkey [email protected] Zeynep Elyas Kaya, MD Elazig Egitim ve Arastirma Hastanesi, Turkey Nesrin Dilbaz, MD Üsküdar Üniversitesi, Turkey Merve Cingi Yirün, MD Ankara Numune Training and Research Hospital, Turkey
http://tpp.sagepub.com 229
Therapeutic Advances in Psychopharmacology 6(3) Case presentation This case report focuses on a 26-year-old woman: a married high-school graduate, housewife, and mother of one, who gave birth 15 months ago. A month ago, she was diagnosed with polycystic ovarian syndrome and subsequently treated with a levonorgestrel-containing intrauterine device. Cabergoline was started at 0.5 mg once per day to stop lactating. Two days after the first dose of cabergoline, the patient complained of irritation, insomnia, and a short temper. She locked her child and herself into a room and then removed everything that might hurt somebody at home. She worried that her child was going to be harmed by a spell that someone had cast on their house. She started to talk to herself and then began arguing with her husband. This led to her later throwing a lot of his belongings away and kicking him out of the house. She also began listening to music at high volume, laughing loudly, and spending much more money than usual. Her religious preoccupations increased. She was not as healthy as usual during that two-week period. In the final week, she even began to neglect her child and her home. She began to think she had some special power. She was laughing loudly, having difficulty sleeping, talking too much, and harming her child in the last few days. The patient was admitted to our emergency room and hospitalized in a psychiatry clinic with the prediagnosis of manic episode with psychotic features. Her mental status examination revealed that the content of her thoughts revealed grandiose and paranoid delusions. She was irritable; her mood was labile and grandiose; and she had a euphoric facial expression. Reality testing was partially impaired. Her judgment and her ability to abstract were also impaired. She exhibited rapid associations, pressured speech, and a flight of ideas. She demonstrated psychomotor hyperactivity and her Young Mania Rating Scale score was calculated as 39. There were no abnormalities in her physical examination and laboratory results. Her cranial MRI was normal. Her dostinex treatment was stopped, and a new treatment was initiated of 20 mg/day of olanzapine, and 600 mg/day of carbamazepine was added as a mood stabilizer. At the end of the second week, the carbamazepine treatment was stopped because of carbamazepineinduced hyponatremia, and a 900 mg/day lithium treatment was started. The psychomotor hyperactivity, irritability, and grandiosity of the patient persisted, and her Young Mania Rating Scale score was 19. Her daily olanzapine dose was increased from 20 to 30 mg. At the end of third
week, her Young Mania Rating Scale score was down to 6. An examination of her mental status showed that her mood was euthymic, her grandiose thoughts had disappeared, and her psychomotor activity was normal. Her elevated mood was significantly improved, as her adaptation to clinical conditions and medications was successful. She was discharged with a treatment regimen of 900 mg/day of lithium and 30 mg/day of olanzapine. During her three weeks of clinical observation, her Clinical Global Impressions-Severity (CGI-S) scores were 5, 3, and 1 for the second, third, and fourth weeks, respectively, and her Clinical Global Impressions- Improvement (CGII) scores were 3, 2, and 1 for the second, third, and fourth weeks, respectively. Discussion Goal-directed actions, antidepressants, distortion of circadian rhythm, seasonal changes of especially spring and autumn, stressful life events, and increased emotional expression are previously shown precipitating factors for hypomanic or manic episodes in susceptible individuals [Proudfoot et al. 2011]. Although it has previously been shown that dopamine agonists have aggravating effects on psychosis in schizophrenic patients [Factor et al. 1995], there is not much information about their inducing effects on mania. This case reviewed a manic episode with psychotic features that emerged after use of cabergoline, a dopaminergic agonist with a half-life of 65 hours. Its effect can last nearly 21 days after usage of a single dose. Therefore, managing its side effects is difficult. In this case, the patient’s symptoms started after two days of a single dose of 0.5 mg cabergoline. The timing of the symptoms and the course of the disorder led us to conclude that this manic episode was induced by cabergoline use. Some studies have been reported that it is safer to use cabergoline than bromocriptine in terms of inducing psychosis. [Di Salle et al. 1983] Therefore cabergoline is more commonly preferred in treatment of hyperprolactinemia. However, this situation is probably due to insufficient number of studies about cabergoline’s neuropsychiatric side effects. Although cabergoline is highly effective in hyperprolactinemia treatment, it may induce hypomanic/manic episodes in susceptible individuals, such as in this case. Risk–benefit ratio should be analyzed with prospective controlled studies in
230 http://tpp.sagepub.com
RN Yuksel, ZE Kaya et al. future and cabergoline must be used carefully in susceptible individuals as much as other dopaminergic agonists Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
Fariello, R. (1998) Pharmacodynamic and pharmacokinetic features of cabergoline. Rationale for use in Parkinson’s disease. Drugs 55: 10–16. Movement Disorder Society (2002) DA agonists-ergot derivatives: cabergoline. Mov Disord 17: S68–S71. Perea, E., Robbins, B. and Hutto, B. (2006) Psychosis related to ropinirole. Am J Psychiat 163: 547–548.
Conflict of interest statement The authors declare that there is no conflict of interest.
Pezzoli, G., Martignoni, E., Pacchetti, C., Angeleri, V., Lamberti, P., Muratorio, A. et al. (1994) Pergolide compared with bromocriptine in Parkinson’s disease: a multicenter, crossover, controlled study. Mov Disord 9: 431–436.
References
Pezzoli, G., Martignoni, E., Pacchetti, C., Angeleri, V., Lamberti, P., Muratorio, A. et al. (1995) A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson’s disease. Neurology 45: S22–S27.
Arnold, G., Gasser, T., Storch, A., Lipp, A., Kupsch, A., Hundemer, H. et al. (2005) High doses of pergolide improve clinical globalimpression in advanced Parkinson’s disease: – a preliminary open label study. Arch Gerontol Geriatr 41: 239–253. Boyd, A. (1995) Bromocriptine and psychosis: a literature review. Psychiatr Quart 66: 87–95. Cavallaro, R., Cocchi, F., Angelone, S., Lattuada, E. and Smeraldi, E. (2004) Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study. J Clin Psychiatr 65: 187–190. Chang, S., Chen, C. and Lu, M. (2008) Cabergolineinduced psychotic exacerbation in schizophrenic patients. Gen Hosp Psychiatr 30: 378–380. Di Salle, E., Ornati, G., Giudici, D. and Britanico, G. (1983) Prolactin-lowering effect of a new ergoline derivative, FCE 21336, in the rat: a comparison with bromocriptine. Acta Endocrinol 103: 265. Factor, S., Molho, E., Podskalny, G. and Brown, D. (1995) Parkinson’s disease: drug-induced psychiatric states. Adv Neurol 65: 115–138.
Proudfoot, J., Doran, J., Manicavasagar, V. and Parker, G. (2011) The precipitants of manic/ hypomanic episodes in the context of bipolar disorder: A review. J Affect Disord 133: 381–387. Rascol, O. (1999) Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson’s disease? J Neur TR S 55: 33–45. Schrag, A., Brooks, D., Brunt, E., Fuell, D., Korczyn, A., Poewe, W. et al. (1998) The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson’s disease. Clin Neuropharmacol 21: 169–175. Storch, A., Trenkwalder, C., Oehlwein, C., Winkelmann, J., Polzer, U., Hundemer, H. et al. (2005) High-dose treatment with pergolide in Parkinson’s disease patients with motor fluctuations and dyskinesias. Parkinsonism Relat D 11: 393–398.
Visit SAGE journals online http://tpp.sagepub.com
SAGE journals
http://tpp.sagepub.com 231
