Differences in Prolactin Elevation and Related Symptoms of Atypical Antipsychotics in Schizophrenic Patients
Abstract
OBJECTIVE: The aim of this cross-sectional study was to investigate the degree and frequency of prolactin (PRL) elevation and related symptoms in patients treated with 3 different atypical antipsychotics: clozapine, olanzapine, and risperidone. METHOD: Twenty-eight patients receiving clozapine, 29 patients receiving olanzapine, and 18 patients receiving risperidone (all meeting DSM-IV criteria for schizophrenia, schizophreni-form disorder, or schizoaffective disorder) were studied. The median daily dose was 400 mg of clozapine, 10 mg of olanzapine, and 3 mg of risperidone. Fasting morning blood samples were analyzed for PRL, and the occurrence of hyper-prolactinemic symptoms in the patients was evaluated. RESULTS: Elevated PRL levels were found in 16 (89%) of the patients receiving risperidone and in 7 (24%) of the patients receiving olanzapine, but in none of the patients receiving clozapine. In addition, there was a significant difference in median PRL level among the treatment groups (p < .0001), in that the PRL level was higher both in the patients treated with risperidone and in the patients treated with olanzapine, compared to those treated with clozapine. Moreover, hyperpro-lactinemic symptoms-menstrual disturbances, galactorrhea, impotence, oligospermia, and decreased libido-were reported in 8 (44%) of the risperidone-treated patients and in 1 (3%) of the olanzapine-treated patients, but in none of the clozapine-treated patients. CONCLUSION: Treatment with risperidone was frequently associated with hyperprolactinemia and related symptoms, whereas the occurrence of PRL elevation and related symptoms was modest in patients receiving olanzapine and nonexistent in those receiving clozapine. Thus, atypical anti-psychotics in therapeutic doses differ with regard to effect on PRL secretion.
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Only few studies have directly compared the sexual functioning associated with different atypical antipsychotics.
“To date, only few studies (534-547) have directly compared the sexual functioning associated with different atypical AP.”
From Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care (2011) · cites this paper as [542]
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DE HERT, M., CORRELL, C. U., BOBES, J., CETKOVICH‐BAKMAS, M., COHEN, D., ASAI, I., DETRAUX, J., GAUTAM, S., MÖLLER, H., NDETEI, D. M., et al. (2011) · World Psychiatry · doi:10.1002/j.2051-5545.2011.tb00014.x · Cited by 2,488 · see citing works
“To date, only few studies (534-547) have directly compared the sexual functioning associated with different”
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“3 Clozapine Clozapine induces little or no PRL elevation [11, 15, 30, 46, 110, 131, 155, 236–240] or is associated with significant decreases of PRL levels (after switching from a PRL-elevating FGA) [102, 241].”
BackgroundPharmacological causes of hyperprolactinemia.
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The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings
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“prolactin (Melkersson, 2005; Mann et al, 2006) Clinical significance of these hormonal changes is”
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A review of the association between antipsychotic use and hyperprolactinaemia
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“Other naturalistic studies find hyperprolactinemia in 89% of risperidone subjects (n=18) (Melkersson, 2005).”
Hyperprolactinemia associated with psychotropics—a review
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“Mean prolactin levels were significantly higher in the risperidone and olanzapinetreated subjects compared to clozapine-treated group (Melkersson, 2005).”
ResultVilar, L., de Freitas, M. C., Naves, L. A., Casulari, L. A., Azevedo, M. F., Montenegro, R. M., Barros, A., Faria, M. D. S., Nascimento, G. C., Lima, J. G., et al. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03346388 · Cited by 133 · see citing works
Antipsychotic-Induced Hyperprolactinaemia
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Psychotropic-Induced Hyperprolactinemia: A Clinical Review
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Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review
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“Compared to most first generation antipsychotics (FGAs) and many second generation antipsychotics (SGAs), CLZ has minimal risk for extrapyramidal symptoms (EPS) (Lindström, 1988; Casey, 1989) and does not induce hyperprolactinemia (Kane et al., 1981; Melkersson, 2005).”
BackgroundNocturnal hormone profiles in patients with schizophrenia treated with olanzapine
Mann, K., Rossbach, W., Müller, M. J., Müller-Siecheneder, F., Pott, T., Linde, I., Dittmann, R. W., & Hiemke, C. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.08.005 · Cited by 78 · see citing works
The Effects of Antipsychotics on Prolactin Levels and Women’s Menstruation
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“The prevalence rate of hyperprolactinaemia in patients on olanzapine has been found to be 68% [49], 28% [37], 40% [29], and 24% [55].”
BackgroundMelkersson, K. I. (2006) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.811 · Cited by 70 · see citing works
Self-citationMiller, R. J. (2009) · Current Neuropharmacology · doi:10.2174/157015909790031184 · Cited by 69 · see citing works
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“Treatment with risperidone in this study was associated with statistically significantly increased mean prolactin levels versus placebo, consistent with previous studies (Halbreich and Kahn 2003; Lieberman et al. 2005; Melkersson 2005).”
ResultMiller, R. M. (2009) · Current Neuropharmacology · doi:10.2174/157015909790031229 · Cited by 67 · see citing works
“This conclusion is supported by the fact that, while classical D2blocking neuroleptics increase blood prolactin levels, an effect also seen during therapy with some atypical antipsychotic agents, this is not found with clozapine or quetiapine [27,53,75,95].”
ResultSexual Dysfunction and Psychotropic Medications
Stimmel, G. L., & Gutierrez, M. A. (2006) · CNS Spectrums · doi:10.1017/s1092852900026730 · Cited by 60 · see citing works
Antipsychotic-Induced Hyperprolactinemia
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“(AAs), but there are within-group differences among the AAs.(3) Aripiprazole, a partial D2 agonist, does not seem to cause hyperprolactinemia.”
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“, 1996; Daniel and Copeland, 2000), but not with amisulpride or risperidone (Kinon et al., 2003; Volavka et al., 2004; Melkersson, 2005).”
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“[63] Hyperprolactinemia-related SDs (menstrual disorders, galactorrhea, impotence, oligospermia and decreased libido) (% of subjects) 44 3”
BackgroundKelly, D. L., Wehring, H. J., Earl, A. K., Sullivan, K. M., Dickerson, F., Feldman, S. M., McMahon, R. P., Buchanan, R. W., Warfel, D. T., Keller, W. R., et al. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-214 · Cited by 45 · see citing works
“Others have used >10 ng/ml in males and >20 in females [12] and yet others have used >15-16 ng/ml in both sexes [13,14].”
BackgroundMethodA comparative study of sexual dysfunction involving risperidone, quetiapine, and olanzapine
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“, 2004; Tandon, 2002) and hyperprolactinaemia (Hamner, 2002; Melkersson, 2005; Volavka et al., 2004; Wudarsky et al., 1999).”
BackgroundManagement of Psychosis Associated With a Prolactinoma: Case Report and Review of the Literature
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“The reported occurrence of HPL among indiv iduals tak ing antipsychotic medication ranges from 42 to 89%.([2-5]) HPL is associated with both short-term and long-term physical and psychological problems, including sexual Shanghai Archives of Psychiatry, 2015, Vol.”
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“…hyperprolactinemia is a well-recognized neuroendocrine response to antipsychotics, particularly in female patients (Seeman, 2004), with the prevalence rates varying from 42% to 89% across different study samples (Halbreich and Kahn, 2003; Johnsen et al., 2008; Melkersson, 2005; Wang et al., 2013).”
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“It has been reported that risperidone presented a high risk of hyperprolactinemia, while olanzapine and ziprasidone showed a relatively low risk (Volavka et al., 2004; Melkersson, 2005; Komossa et al., 2009).”
BackgroundSexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics
Kikuchi, T., Iwamoto, K., Sasada, K., Aleksić, B., Yoshida, K., & Ozaki, N. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.11.016 · Cited by 33 · see citing works
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“Aus der Gruppe der neueren AP führen Amisulprid [48] und Risperidon [31] zu signifikanten Prolaktinerhöhungen.”
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“2 – 7 Hyperprolactinaemia and its consequences are therefore common reasons for non-adherence and treatment discontinuation.”
BackgroundHow Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment
Rubio‐Abadal, E., Cacho, N. D., Saenz-Navarrete, G., Arranz, B., Cambra, R. M., Cuadras, D., Rodante, D., Fehér, C., Roca, M., Barneda, V., et al. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000539 · Cited by 27 · see citing works
“Sexual dysfunction and HPRL were not related to levels of sexual hormones in our study, consistent with previous studies.(13,22,33) Lower PSP scores were related to worse sexual functioning, as the literature relates social and personal impairment to SED.”
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“Over two-thirds of studies reported serum PRL levels (19/30; 63%); of those, 21% (4/19) described data among the overall set of participants enrolled in the study, regardless of the drug-induced HPL status [32, 34, 54, 55].”
BackgroundInfluentialIncreased serum prolactin levels in drug-naive first-episode male patients with schizophrenia
Albayrak, Y., Beyazyüz, M., Beyazyüz, E., & Kuloğlu, M. (2013) · Nordic Journal of Psychiatry · doi:10.3109/08039488.2013.839739 · Cited by 20 · see citing works
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“Our data are also consistent with Melkersson (2005) who reported no increase in the prolactin level in 28 women receiving CLZ.”
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Sexual Side Effects of Antipsychotic Drugs
Bains, S., & Shah, A. A. (2012) · Advances in Pharmacoepidemiology & Drug Safety · doi:10.4172/2167-1052.1000109 · Cited by 14 · see citing works
“Loss of libido was the most frequently reported sexual dysfunction with both haloperidol (58%) and clozapine (50%) in one of the studies [27].”
BackgroundPharmacogenetics of Risperidone Response and Induced Side Effects
Correia, C., & Vicente, A. M. (2007) · Personalized Medicine · doi:10.2217/17410541.4.3.271 · Cited by 14 · see citing works
“In addition, risperidone is more likely than other atypical antipsychotics, including the typical antipsychotic haloperidol [18], to cause persistently elevated prolactin levels [19], which can lead to a broad range of symptoms including galactorrhea, gynecomastia, menstrual disturbances, sexual dysfunction, infertili…”
BackgroundOlanzapine/fluoxetine combination for bipolar depression
Shelton, R. C. (2006) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.6.1.33 · Cited by 13 · see citing works
Metformin in the Treatment of Amisulpride-Induced Hyperprolactinemia: A Clinical Trial
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“The incidence rate of HPRL is as high as 70%–100% in patients taking risperidone, 10%– 40% in patients taking olanzapine and quetiapine, and less than 5% in those taking clozapine with no significant symptoms (Melkersson, 2005; Inder and Castle, 2011).”
BackgroundAttenuation of risperidone-induced hyperprolactinemia with the addition of aripiprazole
Rainka, M. M., Capote, H. A., Ross, C. A., & Gengo, F. M. (2009) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2008.01009.x · Cited by 13 · see citing works
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“In contrast, other atypical antipsychotics, such as clozapine, quetiapine and olanzapine, have shown smaller or transient effects on serum prolactin levels, possibly because their actions at other receptor sites result in relatively less dopamine blockade [2, 4-6 ], or because of a lower peripheral to central distribu…”
BackgroundRabdomiólisis producida por la asociación de sinvastatina y risperidona
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“As a result, some patients treated with antipsychotics develop galactorrhoea, amenorrhea, erectile dysfunction, and osteoporosis over the long term.(2,3) Therefore, hyperprolactinemia is a common reason for stopping treatment.”
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“studies have demonstrated that the treatment of schizophrenia with risperidone may cause a substantial plasma prolactin increase and an unacceptably high incidence of prolactin related symptoms (PRS), such as amenorrhea, galactorrhea, gynecomastia, and sexual dysfunction [8, 9].”
Kelly, D. L., Claxton, A., Bidollari, I., & Du, Y. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114030 · Cited by 11 · see citing works
“Antipsychotics are a common cause of drug-induced hyperprolactinemia (Melkersson, 2005; Volavka et al., 2004).”
The return of fixed combinations in psychiatry: fluoxetine and olanzapine combination
Shelton, R. C. (2006) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.2006.2.2.187 · Cited by 9 · see citing works
“…for D2 receptors and limited problems with extrapyramidal side effects, olanzapine has been shown to significantly elevate Powered by TCPDF (www.tcpdf.org) prolactin, which may cause sexual dysfunction, osteoporosis, amenorrhea, gynecomastia, or galactorrhea (Saito et al 2004; Melkersson 2005).”
Metabolische Nebenwirkungen von Antipsychotika der neuen Generation
Engl, J., Tschoner, A., Laimer, M. W., Rettenbacher, M. A., Fleischhacker, W. W., Patsch, J. R., & Ebenbichler, C. F. (2006) · Wiener klinische Wochenschrift · doi:10.1007/s00508-006-0584-3 · Cited by 10 · see citing works
Management of Psychosis Associated With a Prolactinoma: Case Report and Review of the Literature
Ali, S. N., Miller, K. K., & Freudenreich, O. (2010) · Psychosomatics · doi:10.1176/appi.psy.51.5.370 · Cited by 9 · see citing works
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Internet Assessment of Obsessive-Compulsive Disorder
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Longitudinal study of β2-microglobulin abnormalities in schizophrenia
Chittiprol, S., Venkatasubramanian, G., Neelakantachar, N., Reddy, N. A., Shetty, K. T., & Gangadhar, B. N. (2009) · International Immunopharmacology · doi:10.1016/j.intimp.2009.07.002 · Cited by 6 · see citing works
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“Elevation of PRL with risperidone is common and may be higher than with conventional agents (Henderson et al., 2001; Melkersson, 2005), but the frequency of clinical manifestations may be as low as 10%, and the relationship of symptoms to serum concentrations is considered unclear (Kleinberg et al.”
BackgroundTschoner, A., Engl, J., Rettenbacher, M. A., Kaser, S., Ott, H. W., Fleischhacker, W. W., Patsch, J. R., & Ebenbichler, C. F. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08l04509 · Cited by 7 · see citing works
Antipsychotics-related hyperprolactinaemia among patients with schizophrenia in Maiduguri
Shettima, F. B., Wakil, M., Sheikh, T. L., Abdulaziz, M., Wakawa, I. A., & Beida, O. (2024) · South African Journal of Psychiatry · doi:10.4102/sajpsychiatry.v30i0.2133 · Cited by 6 · see citing works
“2,28,29 When individuals on typical antipsychotics were categorised into high (> 300 mg equivalent of chlorpromazine) and low-dose, hyperprolactinaemia was almost two times more prevalent among individuals on high-dose ( p = 0.000) than those on low dose.”
BackgroundInfluentialFollow-Up Study of a Pharmacovigilance Signal
McCarren, M., Qiu, H., Ziyadeh, N. J., Jiang, R., Wang, Y., & McAfee, A. T. (2012) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318271069d · Cited by 5 · see citing works
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“These findings may be related to the observations that olanzapine does not cause clinically relevant elevation of prolactin levels, which are thought to be responsible for antipsychotic-related sexual side effects (Melkersson, 2005).”
BackgroundPsychiatric illness and psychotropic medication use in epilepsy
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- Authors
- Melkersson, K.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Melkersson, Kristina
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2005-06-15
- Volume
- 66
- Issue
- 06
- Pages
- 761-767
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2041281069
- Cited by
- 98
- References
- 0
- Citations by year
- 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 2 · 2016: 2 · 2015: 5 · 2014: 2 · 2013: 9 · 2012: 8
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- prolactin elevation, hyperprolactinemia, atypical antipsychotics, schizophrenia, clozapine, olanzapine, risperidone, galactorrhea, menstrual irregularity, erectile dysfunction, oligozoospermia, low libido, adverse drug reactions
- MeSH terms
- Olanzapine, Adult, Ambulatory Care, Benzodiazepines, Clozapine, Cross-Sectional Studies, Female, Humans, Hyperprolactinemia, Male, Middle Aged, Prolactin, Schizophrenia, Antipsychotic Agents, Prevalence, Treatment Outcome, Risperidone
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