- Email: [email protected]
“Urinary incontinence secondary to amisulpride Use—A report”
Asian Journal of Psychiatry 29 (2017) 190–191
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Letter to the Editor “Urinary incontinence secondary to amisulpride Use—A report”
MARK
1. Introduction Amisulpride is a second-generation antipsychotic and structurally a substituted benzamide derivative. It preferably binds to dopamine D2/D3 receptors in limbic and not with striatal structures. Acting via a dose-dependent blockade of dopamine receptors, it is effective, for treating both the positive and negative symptoms of psychosis and indicated for the treatment of acute and chronic schizophrenia. Pharmacologically Amisulpride has high affinity for the dopamine D2/D3 receptors and has little or no affinity for serotonin, adrenergic, histaminergic or cholinergic receptors (McKeage and Plosker, 2004). Amisulpride usually has a good safety profile- It is associated with a low propensity for causing extrapyramidal side effects because of its limbic selectivity (Leucht et al., 2002). It is associated with some weight gain, but relatively lesser than other atypical antipsychotics like clozapine, olanzapine and risperidone (Bak et al., 2014). The main concern with amisulpride is Hyperprolactinemia & associated galactorrhoea, gynaecomastia, irregular periods, libido disturbance. Some other reported adverse effects are − drowsiness, insomnia, agitation, anxiety, Nausea, constipation, dry mouth and rarely hypotension and bradycardia (Chabra and Bhatia, 2007). However Urinary incontinence associated with amisulpride seems to be a very rare event that we could find only a single case published in medical literature till date (Mendhekar and Lohia, 2008). Thus hereby we report a case of urinary incontinence associated with Amisulpride. 2. Case presentation Mrs. S a 41 years old, married female was consulted with the department of psychiatry as her family members observed her behaving in an unusual manner gradually over last 8 months. She presented with withdrawn behavior, suspiciousness towards family members, hearing third person auditory hallucinations with persecutory content and associated socio-occupational dysfunction. A diagnosis of paranoid schizophrenia was kept and the patient was started with oral olanzapine 10 mg per day. She responded to that treatment and her active symptoms subsided next few weeks, however patient and her family member complaint of increased sedation and weight gain and discussed for a treatment change as the patient was not willing to comply with her current medication. Thus, the patient was started upon with Amisulpride 400 mg per day in two divided dosages. She maintained the improvement after this treatment change, however, after 2 weeks later she started complaining that she was having passage of urine while sleeping at night, almost every alternate night. For the first week it occurred during night time, but later started during day time as well occasionally and she would become aware after wetting herself. There was no previous history of any incontinence or current urinary complaints like dysuria, hesitancy or significant medical history. Also, there were no recent significant changes in patient’s fluid intake, including caffeine and no history of any other concurrent medications. Her physical and neurological examination was unremarkable also urine microscopy and culture reports came back negative. As patient’s active symptoms were already subsided, we attempted dosage reduction to 200 mg per day, however, it did not help her over incontinence issue. Thus In view of patient’s troublesome embarrassment with this issue, we stopped Amisulpride and monitored her in the inpatient setting. After stopping Amisulpride the incontinence ceased completely and afterwards patient was shifted to Aripiprazole 10 mg per day and maintained the improvement. The Naranjo causality scale (Naranjo et al., 1981) yielded a score of 6 corresponding to the Probable Adverse Drug reaction in Index case. 3. Discussion Urinary Incontinence is a serious and embarrassing event for anyone. It adversely affects quality of life which has implications for patient compliance. Urinary incontinence has been associated in scientific literature with many antipsychotics like − clozapine, olanzapine, risperidone etc. Multiple mechanisms have been described in the pathophysiology of antipsychotic associated incontinence, like −alpha 1 adrenergic blockade induced reduced bladder sphincter tone, decreased dopamine in the basal ganglia and anticholinergic action associated Urinary retention and secondary overflow incontinence (Barnes et al., 2012). However regarding Amisulpride, these mechanisms do not explain the pathophysiology of urinary incontinence, keeping in view its selective action on dopamine receptors. Animal studies have however suggested role of dopamine D1 and D2 receptors in the micturition reflex (Seki et al., 2001). Thus, further research is warranted to explore the underlying pathophysiology and risk factors associated with urinary incontinence induced by Amisulpride. While it is also postulated that psychotic Illness itself may predispose for urinary incontinence (Choudhury and Augustine, 1993), in our case the symptom started when patient was relatively stable in terms of her psychotic symptoms and temporally related to administration and cessation of Amisulpride treatment. Thus Keeping in view that Amisulpride is one of the most commonly prescribed antipsychotics in the world, Clinicians have to be aware about http://dx.doi.org/10.1016/j.ajp.2017.07.010 Received 23 June 2017 1876-2018/ © 2017 Elsevier B.V. All rights reserved.
Asian Journal of Psychiatry 29 (2017) 190–191
Letter to the Editor
this associated probable adverse drug reaction for timely assessment and intervention. Conflict of interest None. References Bak, M., Fransen, A., Janssen, J., van Os, J., Drukker, M., 2014. Almost all antipsychotics result in weight gain: a meta-analysis. zhang XY, ed. PLoS One 9 (4), e94112. http://dx.doi.org/ 10.1371/journal.pone.0094112. Barnes, T.R., Drake, M.J., Paton, C., 2012. Nocturnal enuresis with antipsychotic medication. Br. J. Psychiatry 200, 7–9. Chabra, V., Bhatia, M.S., 2007. Amisulpride: a brief review. Delhi Psychiatry J. 10 (2), 140–143. Choudhury, S., Augustine, M., 1993. Urinary incontinence in acute psychosis. Indian J. Psychiatry 35 (2), 123–125. Leucht, S., Pitschel-Walz, G., Engel, R.R., Kissling, W., 2002. Amisulpride, an unusual atypical antipsychotic: a meta-analysis of randomized controlled trials. Am. J. Psychiatry 159, 180–190. McKeage, K., Plosker, L., 2004. Amisulpride, a review of its use in the management of schizophrenia. CNS Drugs 18 (13), 933–956. Mendhekar, D., Lohia, D., 2008. Urinary incontinence associated with amisulpride. World J. Biol. Psychiatry 7, 1–2. Naranjo, C.A., Busto, U., Sellers, E.M., Sandor, P., Ruiz, I., Roberts, E.A., Janecek, E., Domecq, C., Greenblatt, D.J., 1981. A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 30 (August (2)), 239–245. Seki, S., Igawa, Y., Kaidoh, K., Ishizuka, O., Nishizawa, O., Andersson, K.E., 2001. Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats. Neurourol. Urodyn. 20 (1), 105–113. ⁎
Vijay Niranjan , Koustubh R. Bagul, Ram Ghulam Razdan Department of Psychiatry, Mahatma Gandhi Memorial Medical College, Indore, M.P, India E-mail address: [email protected]
⁎
Corresponding author.
191
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Letter to the Editor “Urinary incontinence secondary to amisulpride Use—A report”
MARK
1. Introduction Amisulpride is a second-generation antipsychotic and structurally a substituted benzamide derivative. It preferably binds to dopamine D2/D3 receptors in limbic and not with striatal structures. Acting via a dose-dependent blockade of dopamine receptors, it is effective, for treating both the positive and negative symptoms of psychosis and indicated for the treatment of acute and chronic schizophrenia. Pharmacologically Amisulpride has high affinity for the dopamine D2/D3 receptors and has little or no affinity for serotonin, adrenergic, histaminergic or cholinergic receptors (McKeage and Plosker, 2004). Amisulpride usually has a good safety profile- It is associated with a low propensity for causing extrapyramidal side effects because of its limbic selectivity (Leucht et al., 2002). It is associated with some weight gain, but relatively lesser than other atypical antipsychotics like clozapine, olanzapine and risperidone (Bak et al., 2014). The main concern with amisulpride is Hyperprolactinemia & associated galactorrhoea, gynaecomastia, irregular periods, libido disturbance. Some other reported adverse effects are − drowsiness, insomnia, agitation, anxiety, Nausea, constipation, dry mouth and rarely hypotension and bradycardia (Chabra and Bhatia, 2007). However Urinary incontinence associated with amisulpride seems to be a very rare event that we could find only a single case published in medical literature till date (Mendhekar and Lohia, 2008). Thus hereby we report a case of urinary incontinence associated with Amisulpride. 2. Case presentation Mrs. S a 41 years old, married female was consulted with the department of psychiatry as her family members observed her behaving in an unusual manner gradually over last 8 months. She presented with withdrawn behavior, suspiciousness towards family members, hearing third person auditory hallucinations with persecutory content and associated socio-occupational dysfunction. A diagnosis of paranoid schizophrenia was kept and the patient was started with oral olanzapine 10 mg per day. She responded to that treatment and her active symptoms subsided next few weeks, however patient and her family member complaint of increased sedation and weight gain and discussed for a treatment change as the patient was not willing to comply with her current medication. Thus, the patient was started upon with Amisulpride 400 mg per day in two divided dosages. She maintained the improvement after this treatment change, however, after 2 weeks later she started complaining that she was having passage of urine while sleeping at night, almost every alternate night. For the first week it occurred during night time, but later started during day time as well occasionally and she would become aware after wetting herself. There was no previous history of any incontinence or current urinary complaints like dysuria, hesitancy or significant medical history. Also, there were no recent significant changes in patient’s fluid intake, including caffeine and no history of any other concurrent medications. Her physical and neurological examination was unremarkable also urine microscopy and culture reports came back negative. As patient’s active symptoms were already subsided, we attempted dosage reduction to 200 mg per day, however, it did not help her over incontinence issue. Thus In view of patient’s troublesome embarrassment with this issue, we stopped Amisulpride and monitored her in the inpatient setting. After stopping Amisulpride the incontinence ceased completely and afterwards patient was shifted to Aripiprazole 10 mg per day and maintained the improvement. The Naranjo causality scale (Naranjo et al., 1981) yielded a score of 6 corresponding to the Probable Adverse Drug reaction in Index case. 3. Discussion Urinary Incontinence is a serious and embarrassing event for anyone. It adversely affects quality of life which has implications for patient compliance. Urinary incontinence has been associated in scientific literature with many antipsychotics like − clozapine, olanzapine, risperidone etc. Multiple mechanisms have been described in the pathophysiology of antipsychotic associated incontinence, like −alpha 1 adrenergic blockade induced reduced bladder sphincter tone, decreased dopamine in the basal ganglia and anticholinergic action associated Urinary retention and secondary overflow incontinence (Barnes et al., 2012). However regarding Amisulpride, these mechanisms do not explain the pathophysiology of urinary incontinence, keeping in view its selective action on dopamine receptors. Animal studies have however suggested role of dopamine D1 and D2 receptors in the micturition reflex (Seki et al., 2001). Thus, further research is warranted to explore the underlying pathophysiology and risk factors associated with urinary incontinence induced by Amisulpride. While it is also postulated that psychotic Illness itself may predispose for urinary incontinence (Choudhury and Augustine, 1993), in our case the symptom started when patient was relatively stable in terms of her psychotic symptoms and temporally related to administration and cessation of Amisulpride treatment. Thus Keeping in view that Amisulpride is one of the most commonly prescribed antipsychotics in the world, Clinicians have to be aware about http://dx.doi.org/10.1016/j.ajp.2017.07.010 Received 23 June 2017 1876-2018/ © 2017 Elsevier B.V. All rights reserved.
Asian Journal of Psychiatry 29 (2017) 190–191
Letter to the Editor
this associated probable adverse drug reaction for timely assessment and intervention. Conflict of interest None. References Bak, M., Fransen, A., Janssen, J., van Os, J., Drukker, M., 2014. Almost all antipsychotics result in weight gain: a meta-analysis. zhang XY, ed. PLoS One 9 (4), e94112. http://dx.doi.org/ 10.1371/journal.pone.0094112. Barnes, T.R., Drake, M.J., Paton, C., 2012. Nocturnal enuresis with antipsychotic medication. Br. J. Psychiatry 200, 7–9. Chabra, V., Bhatia, M.S., 2007. Amisulpride: a brief review. Delhi Psychiatry J. 10 (2), 140–143. Choudhury, S., Augustine, M., 1993. Urinary incontinence in acute psychosis. Indian J. Psychiatry 35 (2), 123–125. Leucht, S., Pitschel-Walz, G., Engel, R.R., Kissling, W., 2002. Amisulpride, an unusual atypical antipsychotic: a meta-analysis of randomized controlled trials. Am. J. Psychiatry 159, 180–190. McKeage, K., Plosker, L., 2004. Amisulpride, a review of its use in the management of schizophrenia. CNS Drugs 18 (13), 933–956. Mendhekar, D., Lohia, D., 2008. Urinary incontinence associated with amisulpride. World J. Biol. Psychiatry 7, 1–2. Naranjo, C.A., Busto, U., Sellers, E.M., Sandor, P., Ruiz, I., Roberts, E.A., Janecek, E., Domecq, C., Greenblatt, D.J., 1981. A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 30 (August (2)), 239–245. Seki, S., Igawa, Y., Kaidoh, K., Ishizuka, O., Nishizawa, O., Andersson, K.E., 2001. Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats. Neurourol. Urodyn. 20 (1), 105–113. ⁎
Vijay Niranjan , Koustubh R. Bagul, Ram Ghulam Razdan Department of Psychiatry, Mahatma Gandhi Memorial Medical College, Indore, M.P, India E-mail address: [email protected]
⁎
Corresponding author.
191