488132 2013
TPP3510.1177/2045125313488132Therapeutic Advances in PsychopharmacologyG L Kashyap and J Nayar
Therapeutic Advances in Psychopharmacology
Ther Adv Psychopharmacol (2013) 3(5) 298–300 DOI: 10.1177/ 2045125313488132 © The Author(s), 2013. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Letter to the Editor
Treatment of clozapine-induced priapism by goserline acetate injection Gursharan Lal Kashyap, Jitendra Nayar, Adnan Bashier and Soosamma Varghese
Abstract: Clozapine (Denzapine) is a treatment for resistant schizophrenia. Among the serious but rare side effects of clozapine are agranulocytosis and priapism. We hereby present the case of a 30-year-old man with a diagnosis of schizophrenia who has spent nearly 12 years of his adult life on various psychiatric in-patient units including open wards, secure units, psychiatric intensive care units and rehab wards. Diagnosed at the age of 15, he only responded to clozapine at the age of 18. Whilst being on clozapine he developed priapism in June 2010 and needed emergency surgical treatment in the form of surgical decompression. He again responded only to clozapine and fortunately he did not redevelop priapism; however, he was readmitted in February 2011 due to relapse, and he remained resistant to other antipsychotics. He was rechallenged with clozapine and recovered, but unfortunately redeveloped priapism which required emergency surgical and medical intervention (goserline acetate and tinzaperin injection). In order to relieve the recurrent priapism, he agreed to continue clozapine and goserline acetate injection. This decision was made by the patient in a compos mentis state. As far as we are aware, this is the first time goserline acetate has been reported as a successful treatment for clozapine-induced priapism. Keywords: clozapine, Denzapine, goserline acetate injection, priapism, resistant schizophrenia
Correspondence to: Gursharan Lal Kashyap, MBBS, DCH, MD, MRCPsych SEPT, Weller Wing, Ampthill Road, Bedford, Bedfordshire, UK gursharan.kashyap@sept. nhs.uk Jitendra Nayar, MBBS, DTCD, MD, MRCPsych Adnan Bashier, MBChB, DIP. Clinical Psychiatry Soosamma Varghese, MBBS, MD, PhD SEPT, Weller Wing, Ampthill Road, Bedford, Bedfordshire, UK
Background Sexual health is a very important issue for a young man, but the treatment of mental illness is more important for a psychiatrist. This case illustrates a desperate young man’s dilemma in which he eventually chose his mental health over his sexual health. We all know that schizophrenia is an illness which if left untreated slowly affects all of the domains of a patient’s life. Most adults want to have an active sexual life, but in rare cases a situation arises when they have to compromise this in exchange for their mental stability. Priapism is a sustained and persistent erection of the penis without any sexual desire or stimulation [Keoghane et al. 2002]. It is a urological emergency [Reif and Výborný, 1993] and if not treated in a timely fashion it can cause permanent damage to the penis resulting in impotence or penile necrosis [Dougherty et al. 2012] and urinary retention. Most typical and atypical antipsychotics can cause priapism [Compton and Miller, 2001]. Priapism has been reported with phenothiazine, paroxetine, fluoxetine and trazodone
[Bertholon et al. 1996]. Citalopram causes clitoral priapism [Berk and Acton, 1997] and penile priapism [Netherlands Pharmacovigilance Center Lareb, 2006]. Cases of reversible [Deirmenjian et al. 1998] and irreversible priapism [Songer and Barclay, 2001] have been reported with olanzapine. The occurrence of priapism as a side effect of atypical antipsychotics is thought to be related to alpha-adrenergic blockage mediated by the alpha receptors in the corpora cavernosa of the penis [Sood et al. 2008]. The first case of priapism caused by clozapine was reported in 1992 [Seftel et al. 1992]. Goserelin acetate is a highly potent agonist of gonadotropin releasing hormone [GnRH, also referred to as luteinizing hormone-releasing hormone (LHRH)] and is mainly used for prostate cancer as it suppresses testosterone levels [Tsukagoshi, 2002]. An optimum level of testosterone is essential for an erection [Mikhail, 2006]. Regular continuous administration of injectable goserelin acetate, which significantly reduces
298 http://tpp.sagepub.com Downloaded from tpp.sagepub.com at MOUNT ALLISON UNIV on November 16, 2015
GL Kashyap, J Nayar et al. testosterone levels, is used in the treatment of stuttering or recurrent priapism [Mulhall et al. 2011,Figure 17.3, p. 267]. Goserline acetate, like any other medication, has side effects. These may be fewer/ milder in some or greater/more severe in others.The common side effects are tumour flare (when given for prostate cancer), bone thinning due to osteoporosis, tiredness, hot flushes, loss of libido and erection difficulties, breast fullness/ tenderness and weight gain (this is not an exhaustive list). Case The case we are reporting is of a 30-year-old Afro-Caribbean man who was diagnosed with schizophrenia at the age of 15 and has spent majority of his life thereafter in mental health institutions. Consumption of illicit drugs had been an integral part of his presentations. Since being diagnosed he has been admitted several times mainly due to his noncompliance with medication, consumption of illicit drugs and lack of insight into his condition. Various typical and atypical antipsychotics were tried but to no effect. He was started on clozapine in 2000 but required repeated admissions due to noncompliance. At every admission he was tried on various antipsychotics but every time responded only to clozapine. In June 2010 he developed priapism for the first time on clozapine (Denzapine) and had to be treated by surgical decompression. Clozapine was discontinued; he became psychotic and was readmitted. After failing to respond to other antipsychotics, he was reinitiated on clozapine and did not develop priapism. He was discharged on clozapine plus amisupliride by the end of 2010. He stopped clozapine and consumed illicit drugs, causing a severe relapse of his schizophrenic illness which resulted in hospital admission in early 2011. He again only responded to clozapine but unfortunately redeveloped priapism, requiring immediate surgical intervention and tinzaparin. Clozapine was stopped and other antipsychotics tried with no benefit. Considering the response to clozapine complicated by repeated and severe episodes of priapism requiring surgical interventions, the consultant urologist advised hormonal treatment to be the most appropriate in his case. With no alternatives left he was finally rechallenged with clozapine, but this time with the concurrent use of goserline acetate injection 3.5 mg SC every 28th day, which relieved him of his priapism and enabled him to continue on clozapine.
The patient recovered fully and was maintained on a combination of clozapine, a minimal dose of amisupliride and 4-weekly injection of 3.5 mg goserline acetate for the next 6 months. He then refused goserline acetate injection but continued with the clozapine. Within a couple of days he again developed priapism and ended up in A&E for emergency surgical intervention. This time he requested, and we tried, to reduce clozapine and we raised the amisulpiride. He became severely psychotic within a week and had to be restarted on clozapine; fortunately he agreed to have 4-weekly goserline acetate injection at the same dose. His psychosis improved and he did not develop priapism. We had a detailed discussion about his illness, medication, side effects of clozapine and treatment of priapism. A formal detailed Capacity Assessment was undertaken and this time he decided to stay on clozapine and goserline acetate injection. He was very well stabilized and discharged into the community on a daily dose of clozapine 500 mg, amisulpiride 400 mg and 4-weekly goserline acetate injection 3.5 mg. Discussion This is the first time that goserline acetate injection has been used successfully to treat priapism resulting from clozapine use in severely resistant schizophrenia. Priapism is one of the rare but dangerous complications of antipsychotics. Clozapine is one of the established drugs for treatment-resistant schizophrenia and as we know that clozapine is used in patients whose illness is resistant to various other antipsychotics, its discontinuation can lead to a quick and severe relapse. At the same time, however, clozapine can cause serious side effects such as priapism, an embarrassing condition which is a urological emergency potentially leading to severe complications as well as lifelong sexual problems. It is very difficult for patients to discuss this in the open ward round settings, especially in the presence of female staff or large numbers of staff members. We have to be aware and mindful of this uncommon, unusual and rare side effect of clozapine which if not severe, might go unnoticed due to the hesitancy of a patient in revealing it. We may have to ask the patients specifically about priapism. It can be a dilemma for doctors to rechallenge with clozapine, and the literature suggests that there have been patients who never redeveloped priapism. At the same time, there can be cases such as ours where the patient developed stuttering
http://tpp.sagepub.com 299 Downloaded from tpp.sagepub.com at MOUNT ALLISON UNIV on November 16, 2015
Therapeutic Advances in Psychopharmacology 3 (5) (recurrent) priapism whenever he was rechallenged with clozapine, as evidenced by a clear temporal relationship of the occurrence of priapism with initiations of clozapine, and its disappearance with the discontinuation of clozapine. In cases such as these where every other antipsychotic has failed, the clinician has to give due consideration to spending time in discussion with the patient and giving them all of the relevant necessary information regarding clozapine (or, for that matter, any other antipsychotic) including information about rare but serious side effects such as priapism and treatments including injectable goserline acetate (and its side effects) which may also affect the natural sexual erection in a sexually viable adult patient. We have to thoroughly check the patient’s capacity to help them make a decision regarding these issues, to empower the patient with knowledge and information, to discuss with them the delicate balance between mental health and sexual health, and to provide them with as much support as possible to make an informed decision. With our patuent, we discussed the side effects of clozapine, the use of goserline acetate, checked his capacity and he willingly agreed to continue the treatment. Recognition and acknowledgement of the patient’s distress are essential, and the issue is a sensitive one requiring time, patience and relevant support for resolution. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors. Conflict of interest statement The author declares that there is no conflict of interest.
References Visit SAGE journals online http://tpp.sagepub.com
SAGE journals
Berk, M. and Acton, M. (1997) Citalopramassociated clitoral priapism: a case series. Int Clin Psychopharmacol 12: 121–122.
Bertholon, F., Krajewsky, Y. and Alli, A. (1996) Adverse effects: priapism caused by paroxetine. Ann Med Psychol 154: 145–147. Compton, M. and Miller, A. (2001) Priapism associated with conventional and atypical antipsychotic medications: a review. J Clin Psychiatr 62: 362–366. Deirmenjian, J., Erhart, S., Wirshing, D., Spellberg, B. and Wirshing, W. (1998) Olanzapineinduced reversible priapism: a case report. J Clin Psychopharmacol 18: 351–353. Dougherty, C., Richard, A. and Carey, M. (2012) Priapism in emergency medicine. emedicine. medscape.com/article/777603-overview (accessed on 16 November 2012). Keoghane, S., Sullivan, M. and Miller, M. (2002) The aetiology, pathogenesis and management of priapism. Br J Urol Int 90: 149–154. Mikhail, N. (2006) Does testosterone have a role in erectile function? Am J Med 119: 373–382. Mulhall, J., Incrocci, L., Goldstein, I. and Rosen, R. (2011) Cancer and Sexual Health. New York: Humana Press. Netherlands Pharmacovigilance Center Lareb (2006) Citalopram and priaprism. https://www. lareb.nl/LarebCorporateWebsite/media/publicaties/ kwb_2006_4_citalopr.pdf (accessed on 16 November 2012). Reif, R. and Výborný, K. (1993) Priapism: a urological emergency. Acta Univ Palacki Olomuc Fac Med 135: 59–63. Seftel, A., Saenz de Tejada, I., Szetela, B., Cole, J. and Goldstein, I. (1992) Clozapine-associated priapism: a case report. J Urol 147: 146–148. Songer, D. and Barclay, J. (2001) Olanzapine-induced priapism. Am J Psychiatr 158: 2087–2088. Sood, S., James, W. and Bailon, M. (2008) Priapism associated with atypical antipsychotic medications: a review. Int Clin Psychopharmacol 23: 9–17. Tsukagoshi, S. (2002) A new LH-RH agonist for treatment of prostate cancer, 3-month controlledrelease formulation of goserelin acetate (Zoladex LA 10.8 mg depot) - outline of pre-clinical and clinical studies. Gan To Kagaku Ryoho 29: 1675–1687.
300 http://tpp.sagepub.com Downloaded from tpp.sagepub.com at MOUNT ALLISON UNIV on November 16, 2015
TPP3510.1177/2045125313488132Therapeutic Advances in PsychopharmacologyG L Kashyap and J Nayar
Therapeutic Advances in Psychopharmacology
Ther Adv Psychopharmacol (2013) 3(5) 298–300 DOI: 10.1177/ 2045125313488132 © The Author(s), 2013. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Letter to the Editor
Treatment of clozapine-induced priapism by goserline acetate injection Gursharan Lal Kashyap, Jitendra Nayar, Adnan Bashier and Soosamma Varghese
Abstract: Clozapine (Denzapine) is a treatment for resistant schizophrenia. Among the serious but rare side effects of clozapine are agranulocytosis and priapism. We hereby present the case of a 30-year-old man with a diagnosis of schizophrenia who has spent nearly 12 years of his adult life on various psychiatric in-patient units including open wards, secure units, psychiatric intensive care units and rehab wards. Diagnosed at the age of 15, he only responded to clozapine at the age of 18. Whilst being on clozapine he developed priapism in June 2010 and needed emergency surgical treatment in the form of surgical decompression. He again responded only to clozapine and fortunately he did not redevelop priapism; however, he was readmitted in February 2011 due to relapse, and he remained resistant to other antipsychotics. He was rechallenged with clozapine and recovered, but unfortunately redeveloped priapism which required emergency surgical and medical intervention (goserline acetate and tinzaperin injection). In order to relieve the recurrent priapism, he agreed to continue clozapine and goserline acetate injection. This decision was made by the patient in a compos mentis state. As far as we are aware, this is the first time goserline acetate has been reported as a successful treatment for clozapine-induced priapism. Keywords: clozapine, Denzapine, goserline acetate injection, priapism, resistant schizophrenia
Correspondence to: Gursharan Lal Kashyap, MBBS, DCH, MD, MRCPsych SEPT, Weller Wing, Ampthill Road, Bedford, Bedfordshire, UK gursharan.kashyap@sept. nhs.uk Jitendra Nayar, MBBS, DTCD, MD, MRCPsych Adnan Bashier, MBChB, DIP. Clinical Psychiatry Soosamma Varghese, MBBS, MD, PhD SEPT, Weller Wing, Ampthill Road, Bedford, Bedfordshire, UK
Background Sexual health is a very important issue for a young man, but the treatment of mental illness is more important for a psychiatrist. This case illustrates a desperate young man’s dilemma in which he eventually chose his mental health over his sexual health. We all know that schizophrenia is an illness which if left untreated slowly affects all of the domains of a patient’s life. Most adults want to have an active sexual life, but in rare cases a situation arises when they have to compromise this in exchange for their mental stability. Priapism is a sustained and persistent erection of the penis without any sexual desire or stimulation [Keoghane et al. 2002]. It is a urological emergency [Reif and Výborný, 1993] and if not treated in a timely fashion it can cause permanent damage to the penis resulting in impotence or penile necrosis [Dougherty et al. 2012] and urinary retention. Most typical and atypical antipsychotics can cause priapism [Compton and Miller, 2001]. Priapism has been reported with phenothiazine, paroxetine, fluoxetine and trazodone
[Bertholon et al. 1996]. Citalopram causes clitoral priapism [Berk and Acton, 1997] and penile priapism [Netherlands Pharmacovigilance Center Lareb, 2006]. Cases of reversible [Deirmenjian et al. 1998] and irreversible priapism [Songer and Barclay, 2001] have been reported with olanzapine. The occurrence of priapism as a side effect of atypical antipsychotics is thought to be related to alpha-adrenergic blockage mediated by the alpha receptors in the corpora cavernosa of the penis [Sood et al. 2008]. The first case of priapism caused by clozapine was reported in 1992 [Seftel et al. 1992]. Goserelin acetate is a highly potent agonist of gonadotropin releasing hormone [GnRH, also referred to as luteinizing hormone-releasing hormone (LHRH)] and is mainly used for prostate cancer as it suppresses testosterone levels [Tsukagoshi, 2002]. An optimum level of testosterone is essential for an erection [Mikhail, 2006]. Regular continuous administration of injectable goserelin acetate, which significantly reduces
298 http://tpp.sagepub.com Downloaded from tpp.sagepub.com at MOUNT ALLISON UNIV on November 16, 2015
GL Kashyap, J Nayar et al. testosterone levels, is used in the treatment of stuttering or recurrent priapism [Mulhall et al. 2011,Figure 17.3, p. 267]. Goserline acetate, like any other medication, has side effects. These may be fewer/ milder in some or greater/more severe in others.The common side effects are tumour flare (when given for prostate cancer), bone thinning due to osteoporosis, tiredness, hot flushes, loss of libido and erection difficulties, breast fullness/ tenderness and weight gain (this is not an exhaustive list). Case The case we are reporting is of a 30-year-old Afro-Caribbean man who was diagnosed with schizophrenia at the age of 15 and has spent majority of his life thereafter in mental health institutions. Consumption of illicit drugs had been an integral part of his presentations. Since being diagnosed he has been admitted several times mainly due to his noncompliance with medication, consumption of illicit drugs and lack of insight into his condition. Various typical and atypical antipsychotics were tried but to no effect. He was started on clozapine in 2000 but required repeated admissions due to noncompliance. At every admission he was tried on various antipsychotics but every time responded only to clozapine. In June 2010 he developed priapism for the first time on clozapine (Denzapine) and had to be treated by surgical decompression. Clozapine was discontinued; he became psychotic and was readmitted. After failing to respond to other antipsychotics, he was reinitiated on clozapine and did not develop priapism. He was discharged on clozapine plus amisupliride by the end of 2010. He stopped clozapine and consumed illicit drugs, causing a severe relapse of his schizophrenic illness which resulted in hospital admission in early 2011. He again only responded to clozapine but unfortunately redeveloped priapism, requiring immediate surgical intervention and tinzaparin. Clozapine was stopped and other antipsychotics tried with no benefit. Considering the response to clozapine complicated by repeated and severe episodes of priapism requiring surgical interventions, the consultant urologist advised hormonal treatment to be the most appropriate in his case. With no alternatives left he was finally rechallenged with clozapine, but this time with the concurrent use of goserline acetate injection 3.5 mg SC every 28th day, which relieved him of his priapism and enabled him to continue on clozapine.
The patient recovered fully and was maintained on a combination of clozapine, a minimal dose of amisupliride and 4-weekly injection of 3.5 mg goserline acetate for the next 6 months. He then refused goserline acetate injection but continued with the clozapine. Within a couple of days he again developed priapism and ended up in A&E for emergency surgical intervention. This time he requested, and we tried, to reduce clozapine and we raised the amisulpiride. He became severely psychotic within a week and had to be restarted on clozapine; fortunately he agreed to have 4-weekly goserline acetate injection at the same dose. His psychosis improved and he did not develop priapism. We had a detailed discussion about his illness, medication, side effects of clozapine and treatment of priapism. A formal detailed Capacity Assessment was undertaken and this time he decided to stay on clozapine and goserline acetate injection. He was very well stabilized and discharged into the community on a daily dose of clozapine 500 mg, amisulpiride 400 mg and 4-weekly goserline acetate injection 3.5 mg. Discussion This is the first time that goserline acetate injection has been used successfully to treat priapism resulting from clozapine use in severely resistant schizophrenia. Priapism is one of the rare but dangerous complications of antipsychotics. Clozapine is one of the established drugs for treatment-resistant schizophrenia and as we know that clozapine is used in patients whose illness is resistant to various other antipsychotics, its discontinuation can lead to a quick and severe relapse. At the same time, however, clozapine can cause serious side effects such as priapism, an embarrassing condition which is a urological emergency potentially leading to severe complications as well as lifelong sexual problems. It is very difficult for patients to discuss this in the open ward round settings, especially in the presence of female staff or large numbers of staff members. We have to be aware and mindful of this uncommon, unusual and rare side effect of clozapine which if not severe, might go unnoticed due to the hesitancy of a patient in revealing it. We may have to ask the patients specifically about priapism. It can be a dilemma for doctors to rechallenge with clozapine, and the literature suggests that there have been patients who never redeveloped priapism. At the same time, there can be cases such as ours where the patient developed stuttering
http://tpp.sagepub.com 299 Downloaded from tpp.sagepub.com at MOUNT ALLISON UNIV on November 16, 2015
Therapeutic Advances in Psychopharmacology 3 (5) (recurrent) priapism whenever he was rechallenged with clozapine, as evidenced by a clear temporal relationship of the occurrence of priapism with initiations of clozapine, and its disappearance with the discontinuation of clozapine. In cases such as these where every other antipsychotic has failed, the clinician has to give due consideration to spending time in discussion with the patient and giving them all of the relevant necessary information regarding clozapine (or, for that matter, any other antipsychotic) including information about rare but serious side effects such as priapism and treatments including injectable goserline acetate (and its side effects) which may also affect the natural sexual erection in a sexually viable adult patient. We have to thoroughly check the patient’s capacity to help them make a decision regarding these issues, to empower the patient with knowledge and information, to discuss with them the delicate balance between mental health and sexual health, and to provide them with as much support as possible to make an informed decision. With our patuent, we discussed the side effects of clozapine, the use of goserline acetate, checked his capacity and he willingly agreed to continue the treatment. Recognition and acknowledgement of the patient’s distress are essential, and the issue is a sensitive one requiring time, patience and relevant support for resolution. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors. Conflict of interest statement The author declares that there is no conflict of interest.
References Visit SAGE journals online http://tpp.sagepub.com
SAGE journals
Berk, M. and Acton, M. (1997) Citalopramassociated clitoral priapism: a case series. Int Clin Psychopharmacol 12: 121–122.
Bertholon, F., Krajewsky, Y. and Alli, A. (1996) Adverse effects: priapism caused by paroxetine. Ann Med Psychol 154: 145–147. Compton, M. and Miller, A. (2001) Priapism associated with conventional and atypical antipsychotic medications: a review. J Clin Psychiatr 62: 362–366. Deirmenjian, J., Erhart, S., Wirshing, D., Spellberg, B. and Wirshing, W. (1998) Olanzapineinduced reversible priapism: a case report. J Clin Psychopharmacol 18: 351–353. Dougherty, C., Richard, A. and Carey, M. (2012) Priapism in emergency medicine. emedicine. medscape.com/article/777603-overview (accessed on 16 November 2012). Keoghane, S., Sullivan, M. and Miller, M. (2002) The aetiology, pathogenesis and management of priapism. Br J Urol Int 90: 149–154. Mikhail, N. (2006) Does testosterone have a role in erectile function? Am J Med 119: 373–382. Mulhall, J., Incrocci, L., Goldstein, I. and Rosen, R. (2011) Cancer and Sexual Health. New York: Humana Press. Netherlands Pharmacovigilance Center Lareb (2006) Citalopram and priaprism. https://www. lareb.nl/LarebCorporateWebsite/media/publicaties/ kwb_2006_4_citalopr.pdf (accessed on 16 November 2012). Reif, R. and Výborný, K. (1993) Priapism: a urological emergency. Acta Univ Palacki Olomuc Fac Med 135: 59–63. Seftel, A., Saenz de Tejada, I., Szetela, B., Cole, J. and Goldstein, I. (1992) Clozapine-associated priapism: a case report. J Urol 147: 146–148. Songer, D. and Barclay, J. (2001) Olanzapine-induced priapism. Am J Psychiatr 158: 2087–2088. Sood, S., James, W. and Bailon, M. (2008) Priapism associated with atypical antipsychotic medications: a review. Int Clin Psychopharmacol 23: 9–17. Tsukagoshi, S. (2002) A new LH-RH agonist for treatment of prostate cancer, 3-month controlledrelease formulation of goserelin acetate (Zoladex LA 10.8 mg depot) - outline of pre-clinical and clinical studies. Gan To Kagaku Ryoho 29: 1675–1687.
300 http://tpp.sagepub.com Downloaded from tpp.sagepub.com at MOUNT ALLISON UNIV on November 16, 2015
