Hyperprolactinemia-Related Adverse Events Associated with Antipsychotic Treatment in Children and Adolescents
Article Outline
Abstract
Purpose
To characterize factors related to the development of hyperprolactinemia and the ensuing reproductive/sexual adverse events in children and adolescents treated with antipsychotic and other psychotropic agents, and the additional risk posed for those with comorbid obesity, metabolic, or endocrine disorders.
Methods
A retrospective cohort design evaluating medical and pharmacy claims from South Carolina's Medicaid program was used to compare incidence rates for sexual/reproductive adverse events in 4140 children and adolescents who were newly prescribed one of six atypical or two conventional antipsychotic medications, and a random sample of 4500 children not treated with psychotropic medications, January 1998 to December 2005. Logistic and Cox Proportional Hazards regression and Kaplan-Meier survival analysis were performed.
Results
The treated cohort was not significantly more likely to evince hyperprolactinemia-related disorders than the control sample, but females and adolescents 13 and older were. Incident reproductive/sexual conditions were more likely for females (odds ratio [OR] = 9.52; confidence interval [CI] = 7.63–11.90), adolescents (OR = 3.91; CI = 3.25–4.70), those also taking selective serotonin reuptake inhibitors (SSRIs) (OR = 2.04; CI = 1.56–2.37) or valproic acid derivatives (OR = 1.29; CI = 1.03–1.64), and those with comorbid obesity/weight gain (OR = 1.92; CI = 1.56–2.37), metabolic (OR = 1.41; CI = 1.12–1.78), or endocrine disorders (OR = 2.76; CI = 1.98–3.84).
Conclusion
In this treated cohort, female adolescents exposed to SSRIs or valproic acid derivatives and those with comorbid obesity, metabolic, or endocrine disorders while taking antipsychotics were at higher risk of developing hyperprolactinemia and ensuing sexual/reproductive adverse events.
Keywords: Antipsychotics, Antidepressants, Anticonvulsants, Sexual side effects, Adolescents
Hyperprolactinemia can be induced by physiologic, pharmacologic, and pathologic causes [1]. Normal prolactin (PRL) secretion levels may be changed because of pregnancy, lactation, physical stress, and psychological stress [1], [3]. Regulation of PRL secretion is quite complex, involving disparate substances, such as neurotransmitters, neurohormones, neuropeptides, metabolic substrates, and systemic hormonal signals [1], [2]. Neurotransmitters regulate PRL secretion through the central nervous system at the hypothalamic and tuberoinfundibular dopaminergic system levels. Inhibitory neurotransmitters, for example, serotonin and norepinephrine, increase PRL secretion by decreasing tuberoinfundibular dopaminergic activity. Treatment with dopamine receptor antagonist drugs also induces hyperprolactinemia, via the dopaminergic inhibition of PRL secretion [1], [2]. These drugs include conventional and second-generation antipsychotic (SGA) medications, antidepressants (tricyclic, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors [SSRIs]), opiates, cocaine, gastrointestinal medications, and antihypertensives [4], [5]. Medication-induced hyperprolactinemia inhibits the release of hypothalamic gonadotropin-releasing hormone, which in turn, inhibits the release of luteinizing and follicle-stimulating hormones from the pituitary, leading to suppression of ovarian and testicular function, and reduced sex-steroid production [6].
More generally, serotonin, dopamine, and noradrenaline neurotransmitters regulate a wide variety of appetitive processes, and mediate feeding behavior, which are associated with obesity, insulin secretion and insulin resistance, and lipid homeostasis (through their linkage with body weight changes) [7]. Early-onset, nonpharmacologic-induced obesity has its own significant effect on the general health of the children affected: impaired glucose tolerance, hyperinsulinism, type 2 diabetes mellitus, polycystic ovary syndrome, dyslipidemia (hypercholesterolemia, hyperlipidemia, and so forth), and hypothyroidism [8].
Psychiatric disorders are commonly diagnosed in the pediatric and adolescent population. Antipsychotics, especially SGAs, have been increasingly used for treatment of these disorders over the past decade [9], [10], [11]. Both conventional and some SGAs elevate prolactin levels, resulting in sexual/reproductive side effects such as menstrual irregularities/dysfunction in females [12] and erectile dysfunction in males [2]. Although conventional antipsychotics, such as haloperidol, raise serum prolactin levels, SGAs are more variable in their effects, with some being more likely to elevate serum prolactin levels, namely risperidone, and the others being much less likely to change these levels or to reverse previous medication-induced elevations of prolactin, for example, aripiprazole or ziprasidone [2], [4], [6], [12], [13], [14], [15].
Elevated prolactin levels can also lead to decreased libido, hirsutism, breast symptoms/gynecomastia, or galactorrhea in both genders. Furthermore, elevated prolactin levels in adolescents may be associated with obesity, infertility, and osteoporosis later in life [16]. These reproductive/sexual adverse events have been documented in both adult and child/adolescent populations [2], [17], [18], [19], [20]. However, the hyperprolactinemia effect may be more pronounced in postpubertal children and adolescents than in adults, prepubertal females, or males of any age [20]. Sexual/reproductive side effects are not highly correlated with serum prolactin levels, so not all patients who have hyperprolactinemia develop these side effects [2], [18].
Pediatric and adolescent psychiatric disorders are often treated concomitantly with SGAs and antidepressants or mood stabilizers. Common side effects of the SSRIs include hyperprolactinemia, and the ensuing reproductive/sexual side effects [21], [22], such as galactorrhea, and gynecomastia [23]. Premarketing clinical trials indicate that SSRIs have a positive, sometimes dose-related, effect on a range of sexual/reproductive events: ejaculation delay (2%–28%), impotence/erectile dysfunction (1%–8%), decreased libido (5%–7%), anorgasmia (1%–10%), menstrual disorders (<1%–5%), and hyperprolactinemia (<1%–2%) ([24], [25]; manufacturer's labeling for each agent). Moreover, postmarketing clinical reports provide increasing evidence that treatment with SSRIs may induce sexual side effects, the frequency of which is much higher than reported during clinical trials [26]. The SSRIs are more likely to cause long-term reproductive dysfunction than the newer serotonin and norepinephrine reuptake inhibitors (duloxetine, venlafaxine), heterocyclics (mirtazapine, nefazadone), trazadone, or bupropion [27], [28]. Anticonvulsant valproic acid derivatives used for mood stabilization are associated also with the menstrual dysfunction and hirsutism in polycystic ovary syndrome, especially in African Americans, and those with obesity, insulin resistance, and dyslipidemia [27].
It is very important, therefore, to characterize the adverse impact of these SGAs on the developing child. Consideration should also be given to young populations exposed to these medications with pre-existing medical conditions and on other psychopharmacologic agents. In this analysis, we compare the development of incident reproductive adverse events after antipsychotic treatment was initiated in 4140 children and adolescents with a random sample of children served through Medicaid with no exposure to psychotropic medications. We also examine the additional risk posed for these children for developing reproductive/sexual events when they have comorbid obesity, endocrine, or metabolic disturbances, as well as the added risk of being prescribed SSRIs or valproic acid derivatives for concomitant psychiatric disorders.
Methods
Claims data for South Carolina's Medicaid program were obtained through the state Office of Research and Statistics. Data from both medical and pharmacy claims were used, with encrypted patient demographics and identifiers to protect patient confidentiality. Each Medicaid medical claim identifies a service encounter, and gives the date of service, and the International Classification of Diseases (ICD), Ninth Revision, diagnosis codes related to that visit (Visit file). Pharmacy claims identified the medication dispensed, and the date the prescription was filled (Pharmacy file). A separate data file on eligibility was used to compile the demographic for each patient (Person file). Data in these databases are routinely compiled and cleaned prior to being made available for analysis. This study was approved by the University of South Carolina institutional review board as exempt from human subject research guidelines under 45 Code of Federal Regulations part 46.
Medical and pharmacy claims for the calendar years January 1, 1996 through December 31, 2005 were used to identify a cohort of child and adolescent patients (0–17) enrolled in and eligible for Medicaid for a minimum of 9 months in each calendar year included in this analysis, who had service encounters, and were prescribed haloperidol, fluphenazine, or one of five atypical antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, or olanzapine), between January 1, 1998 and December 31, 2003. The date of first prescription of an antipsychotic medication in the Medicaid file was defined as the selection encounter date.
Out of the same population and from the same time period, medical and pharmacy claims were also used to identify a randomly selected group of child and adolescent patients (0–17 years old) eligible for Medicaid 9 out of 12 months in all calendar years under study, who had service encounters, but no prescriptions in the database for any class of psychotropic medication (antipsychotics, antidepressants, mood stabilizers, or psychostimulants). This process resulted in the identification of 40,660 patients who met the criteria. From this group, a random sample of 4500 patients was selected to use as a representative control group.
Adverse event coding
Reproductive/sexual medical conditions that were detected in the 24 months prior to each patient's selection encounter date were coded as “preexisting” for this study. If the patient developed a reproductive/sexual medical condition subsequent to the prescription of the antipsychotic medication, new variables were created for these “incident” events. The following categories of conditions and events were evaluated: amenorrhea, oligomenorrhea, erectile dysfunction, pituitary disorders including hyperprolactinemia, irregular menses, gynecomastia, or galactorrhea. Obesity and excessive weight gain were coded as one category, whereas dyslipidemia and type 2 diabetes mellitus were coded together as another “metabolic disruption” category. “Other endocrine disorders” were coded as one category as well: parathyroid, pituitary, thymus, and adrenal gland disorders; ovarian dysfunction and failure; testicular and polyglandular dysfunction; delayed or precocious sexual development; carcinoid syndrome; ectopic hormone secretion; dwarfism; pineal gland dysfunction; Werner's syndrome; and unspecified endocrine disorders. In preparation for the statistical analysis, a diagnosis of one of these adverse events was detected first on one or more services in the Visits file and was then dichotomously recoded as “present” for an individual on the unduplicated Person file.
Statistical analyses
One multiple logistic regression equation was constructed to assess the relative odds associated with having sexual/reproductive conditions (combined pre-existing prevalence and incidence rates), using the control group as the primary comparator, and controlling for three individual risk factors (i.e., gender, ethnicity, and age), dichotomously coded as male/female, African American/other, and age equal to or less than 2/age equal to or more than 13. Another multiple logistic regression equation was then constructed to assess the relative odds associated with developing reproductive/sexual adverse events, using the antipsychotic medications as predictors (with olanzapine as the comparator), and controlling for three individual risk factors (i.e., gender, ethnicity, and age), dichotomously coded as male/female, African American/non-African American, and age equal to or less than 12/age equal to or more than 13 at initiation of antipsychotic medication. Risperidone was the most frequently prescribed antipsychotic in the database as both monotherapy and as polypharmacotherapy; therefore, olanzapine was chosen as the primary comparator to avoid comparing risperidone to itself.
To the second logistic regression equation were added five independent variables coded for comorbid obesity, metabolic disruption, and other endocrine disorders, as well as concomitant use of antidepressants and mood stabilizing medications for predicting which children would develop hyperprolactinemia and/or reproductive/sexual side effects. Antidepressants were categorized as SSRIs for citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Divalproex was coded as the mood stabilizer of interest compared to all other mood stabilizers.
Time elapsed between the prescription of an antipsychotic medication and the first diagnosis of reproductive conditions was assessed using Kaplan-Meier survival analysis, and Cox Proportional Hazards (PH) model regression was then used to determine whether there were differences in time elapsed, using the antipsychotic medications as predictors (with olanzapine as the comparator), and controlling for the three individual risk factors (gender, ethnicity, and age).
Results
Table 1 presents descriptive information about the treated cohort selected, which was 68% male, 41% African American, predominantly affective disorders (55%) with comorbid attention-deficit/hyperactivity disorder (78%), whereas the control sample demographics were quite different: 43.8% male, 75.7% African American, and 18.7% Caucasian. The treated cohort contained a higher percentage of youth with obesity/excessive weight gain and other endocrine disorders, whereas the control group evinced a higher rate of metabolic disruption. Although the clients in the treated cohort were about 3 years older at selection into the cohort (start date of the antipsychotic medication) than those in the control sample, data were compiled on the treated cohort for 2 years prior to their selection date for analysis of the preexisting conditions, making their average age at start date in the data set more comparable to the control group (8.4 years). Furthermore, the control group was observed in the Medicaid data set for an average of 7.6 years, compared to the treated group being observed in it, on average, 7.4 years. Therefore, both the treated cohort and control sample provide an adequate time period for examining longitudinal differences in types of conditions developing over time. These demographic (individual risk factor) differences between the treated cohort and the control sample were incorporated into the multivariate statistical analyses.
Table 1. Descriptive analysis of the cohort of 4140 youths prescribed antipsychotic medications
| Indicator | N or mean | % or SD | N or mean | % or SD |
|---|---|---|---|---|
| Gender | ||||
 Male | 2825 | 68.2% | 1972 | 43.8% |
| Female | 1315 | 31.8% | 2528 | 56.2% |
| Race | ||||
| Caucasian | 1722 | 42% | 842 | 18.7% |
| African American | 1680 | 41% | 3405 | 75.7% |
| Hispanic | 13 | .2% | 42 | .9% |
| Asian | 6 | .1% | 9 | .2% |
| Unknown, mixed | 715 | 17.3% | 202 | 4.5% |
| Age at selection | 10.4 years | SD: 3.6 | 7.2 years | SD: 3.7 |
| Comorbid disorders | ||||
| Comorbid endocrine disorders | 181 | 4.4% | 103 | 2.3% |
| Comorbid obesity/weight gain | 680 | 17.1% | 388 | 8.6% |
| Comorbid type 2 diabetes/dyslipidemia | 404 | 9.8% | 543 | 12.1% |
| Psychiatric diagnoses | ||||
| Schizophrenia (295) | 358 | 8.7% | ||
| Major affective disorders (296) | 2261 | 54.6% | ||
| Other psychotic disorders (297-298) | 1149 | 27.8% | ||
| Conduct disorder or oppositional defiant disorder (312) | 2970 | 71.7% | ||
| Attention-deficit/hyperactivity disorder (ADHD) (314) | 3258 | 78.7% | ||
| Concomitant psychotropic medications | ||||
| Antidepressants: SSRIs | 2367 | 57.2% | ||
| Mood stabilizers: Divalproex | 1703 | 41.1% | ||
In the treated cohort, the number of cases in each of the monotherapy medication groups was as follows: aripiprazole (n = 38; .9%), ziprasidone (n = 87; 2.1%), quetiapine (n = 266; 6.4%), risperidone (n = 1634; 39.5%), olanzapine (n = 326; 7.9%), and haloperidol (n = 32; .8%). One additional medication group had to be created because there was overlap in the medications prescribed: 1756 patients (42.3%) were prescribed more than one SGA or an SGA and a conventional agent during the follow-up period (either sequentially or as concomitant pharmacotherapy with an overlap of more than 30 days). Seventy-four percent of the cohort on multiple antipsychotic medications was treated sequentially, whereas 26% was treated using concomitant pharmacotherapy. Thirty-five percent of the children were treated briefly (1 to 5 months) with an antipsychotic medication, and 65% were treated long-term (6 to 90 months). Concomitant psychotropic medications were prescribed as follows: 57% prescribed an SSRI antidepressant, and 46% prescribed a mood stabilizer.
Dosages in the risperidone group ranged from 0.25 mg to 4 mg, mode = 0.5 or 1 mg, and females were likely to be prescribed higher doses. In the olanzapine group, doses ranged from 2.5 mg to 20 mg, mode = 2.5 or 5 mg. For quetiapine, the doses ranged from 25 mg to 300 mg, mode = 25 mg or 100 mg, and a higher percentage of females were on the medication at every dosage. Aripiprazole doses ranged from 5 mg to 30 mg, mode = 5 mg or 10 mg, and a slightly higher percentage of males were consistently prescribed the higher doses, and ziprasidone doses ranged from 20 mg to 80 mg, mode = 20 mg or 40 mg, with a consistently higher percentage of females being prescribed each dosage.
The combined preexisting prevalence (N = 117, 2.8%) and incidence (N = 343, 8.5%) rate for reproductive/sexual conditions in the treated cohort was somewhat higher than their prevalence rate in the control sample (N = 296, 6.6%). Reproductive/sexual problems developing in the control sample from physiologic or pathologic causes were: amenorrhea (N = 164; 3.6%); oligomenorrhea (N = 7; .2%); irregular menstrual cycle (N = 94; 2.1%); galactorrhea (N = 1; 0.02%); hyperprolactinemia/other pituitary disorders (N = 2; .04%); gynecomastia (N = 61; 1.4%), with no diagnosed impotence/erectile dysfunction. Reproductive/sexual problems developing in the cohort receiving antipsychotic or other psychotropic medication were: amenorrhea (N = 249; 6.0%); oligomenorrhea (N = 20; .5%); irregular menstrual cycle (N = 181; 4.4%); galactorrhea (N = 47; 1.1%); hyperprolactinemia/other pituitary disorders (N = 30; .7%); gynecomastia (N = 72; 1.7%), and no diagnosed impotence/erectile dysfunction.
Table 2 presents statistical comparisons of the treated cohort and untreated control sample, controlling for psychotropic medications, comorbid obesity, metabolic disruption, and other endocrine disorders, as well as the individual risk factors (age, gender, and ethnic) for the reproductive/sexual adverse events examined. The cohort treated with antipsychotic medications was not significantly more likely to evince hyperprolactinemia and ensuing reproductive/sexual disorders, but females and adolescents aged 13 and older were. In the treated cohort, the odds of developing reproductive/sexual adverse events were higher for those taking SSRI or valproic acid derivative (mood stabilizing) medications, and those with comorbid obesity/weight gain, metabolic conditions (type 2 diabetes and dyslipidemia), and other endocrine disorders.
Table 2. Adjusted odds ratios for incident hyperprolactinemia and ensuing reproductive/sexual events related to SGAs, comorbid conditions, and concomitant medications
| Parameter | Odds ratio | 95% Confidence intervals |
|---|---|---|
| Control sample | 1.18 | |
| Female | 9.52∗∗ | 7.63–11.90 |
| African American | 1.10 | |
| Age 13 & over | 3.91∗∗ | 3.25–4.70 |
| Aripiprazole | 1.67 | |
| Ziprasidone | 0.71 | |
| Risperidone | 1.10 | |
| Quetiapine | 1.16 | |
| Haloperidol or Fluphenazine | 1.42 | |
| Multiple antipsychotics | 1.35 | |
| Taking valproic acid derivative | 1.29∗ | 1.03–1.64 |
| Taking SSRI | 2.04∗∗ | 1.56–2.37 |
| Preexisting endocrine condition | 2.76∗∗ | 1.98–3.84 |
| Comorbid obesity | 1.92∗∗ | 1.56–2.37 |
| Comorbid metabolic disruption | 1.41∗ | 1.12–1.78 |
∗Significant at p = .05 or less; |
∗∗significant at p < .0001. |
For those developing sexual/reproductive adverse events, the mean age of initiation of the antipsychotic medication was 13.4 years (SD = 2.4), whereas the mean age of onset of hyperprolactinemia and reproductive/sexual adverse events was 15.1 years (SD = 2.1). The mean time elapsed between initiation of antipsychotic medication and incident hyperprolactinemia or reproductive/sexual adverse event was 25.7 months. Results from the Cox PH regression model showed a significantly shorter time elapsed from start of the antipsychotic to onset of hyperprolactinemia and reproductive/sexual adverse events for adolescents (Wald χ2 = 54.89; p < .0001; hazard ratio [HR] = 2.14; confidence interval [CI] = 1.75, 2.61), but no significant difference in time elapsed for those also exposed to SSRIs or valproic acid derivatives.
Discussion
In this community-based service investigation, 11% of the children and adolescents treated with antipsychotics and adjunctive antidepressant medications developed some type of reproductive/sexual problems compared to 7% of the control sample. Because much less than 1% of either the treated cohort or the control sample was diagnosed with hyperprolactinemia, we infer that almost no laboratory testing is being performed to monitor the development of hyperprolactinemia in either group. We are also concerned that sexual and reproductive issues are not being systematically assessed by primary or specialty care providers even though the association between some antipsychotics, SSRIs, or valproic acid derivatives and hyperprolactinemia or its ensuing sexual and reproductive adverse effects are very well characterized in adults and children [4], [6], [7], [9], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Furthermore, all but three of those affected were female, although 68% of the cohort was male, which may indicate more underreporting or less systematic assessment of sexual adverse events among young males.
Onset of hyperprolactinemia and ensuing reproductive/sexual problems, as defined in this data set, was about 2 years after initiation of the antipsychotic medication in adolescence. This time frame is typical for the onset of menstrual irregularities/disorders in adolescents. Those at highest risk of developing adverse reproductive/sexual events were adolescents, those taking SSRIs or valproic acid derivatives, and those with comorbid obesity/weight gain, metabolic, and other endocrine disorders. Because comorbid disorders, such as glucose intolerance, pituitary dysfunction, or hypothyroidism, are independently linked with reproductive/sexual adverse events through neurotransmitter regulation, it is uncertain whether this cohort would have developed reproductive/sexual dysfunction regardless of exposure to psychotropic medications, but the presence of comorbid obesity, metabolic disruption, and pre-existing endocrinopathies should be considered an important factor in assessing the tolerability and safety of psychotropic medications in children and adolescents.
The pattern of hyperprolactinemia and reproductive/sexual adverse events captured in this study was similar to those found in previous clinical trials and case reports [9], [17], [18], [19], [20], and was more pronounced in postpubertal adolescents [20]. No specific antipsychotic medication increased the risk of these adverse effects in this study, although previous investigations have demonstrated that haloperidol and risperidone can substantially elevate prolactin levels, resulting in sexual side effects in both genders [4], [17], [18], [19], [20]. Speculatively, this finding might be related to the very infrequent use of haloperidol in this cohort, and the low modal dose of risperidone (0.5–1 mg) prescribed, although females were prescribed somewhat higher doses, and the prescription of quetiapine, ziprasidone, and aripiprazole, which are prolactin-sparing or reversing, to these patients over the course of the study period [4], [12], [20], [29]. Extant results also suggest that childhood hyperprolactinemia is dose dependent, normalizes over time, and resolves with discontinuation of the treatment agent [12], [17]. In this cohort, some cases may not have come to the attention of a treating physician and been diagnosed prior to a dose or medication change that normalized any incident hyperprolactinemia.
Administration of SSRIs and valproic acid derivatives has also been documented to cause various hyperprolactinemia and reproductive/sexual adverse effects [21], [22], [23], [26]. In this cohort, exposure to both SSRIs and valproic acid derivatives was associated with increased the risk of developing hyperprolactinemia and reproductive/sexual adverse events among these youth. As reports from postmarketing clinical practice demonstrate, the reproductive/sexual side effects of SSRIs are substantially higher than indicated in the premarketing clinical trials, and the U.S. Food and Drug Administration is considering changing the labeling of SSRIs to reflect a higher frequency of drug-induced sexual adverse events [26]. Previous results indicate that about 20% of women taking valproic acid derivatives experience menstrual dysfunction, breast symptoms, or thyroid function [30]. Thus, the coadministration of SSRIs and some antipsychotic agents (e.g., risperidone and haloperidol) should be considered an important factor in developing hyperprolactinemia and reproductive/sexual adverse effects. Although its neuroendocrine threat appears somewhat less disruptive than for SSRIs, coadministration valproic acid derivatives should still be considered an important factor in selecting and monitoring psychotropic medications.
There are several methodological issues that limit the inferences and interpretations that can be drawn from this analysis: (a) some of the medication “exposure” groups were small, that is, less than 5% of the cohort (i.e., conventionals, aripiprazole, and ziprasidone), but we have chosen to leave these groups in the logistic regression equations as controls, even though they are very small and could skew the results; (b) a research diagnostic interview was not employed to confirm the psychiatric or medical diagnoses; (c) the reporting of adverse events was based on spontaneous reporting to a physician and is, consequently, likely to be an underestimate; (d) these data report associations and, as a result, directions of causality cannot be inferred; (e) key risk factors, such as family history of obesity and endocrine or menstrual disorders, were not available in the database and are not modeled in these analyses; and (f) the cohort was a retrospectively ascertained with data that are reflective of community practice prescribing behavior.
However, the findings draw further attention to the safety profile of antipsychotics and the coprescription of other psychotropic medications in young populations and are germane to the overall appraisal of the benefits and risks of this class of agents. The need for proactive assessment and systematic monitoring of sexual/reproductive symptoms in all age and both gender groups of patients, the value of prolactin-level monitoring/measurement, and management that includes lowering the dose of medication, or switching to lower risk medications as monotherapy or combined therapy, should be underscored by these results. When evaluating the overall benefit–risk ratio of antipsychotics in children and adolescents, the practitioner needs to pay careful consideration to the possible reproductive/sexual ramifications, in both females and males, and individuals with comorbid obesity and endocrine conditions or those receiving concomitant SSRI or valproic acid derivative medications. Given the prevalence of reproductive/sexual adverse events in pediatric and adolescent females treated with antipsychotic medication, including specialists in women's health in the care of these patients, can lead to expeditious diagnosis and management of any reproductive dysfunction that may ensue.
Acknowledgments
Data analysis was supported by a State Mental Health Data Infrastructure Grant (SAMHSA SM54192). The authors thank Ling Li, MSPH, for performing the analyses presented herein. The views expressed do not necessarily represent those of the funding agency or official findings of the SC Department of Health and Human Services (Medicaid).
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PII: S1054-139X(08)00679-4
doi:10.1016/j.jadohealth.2008.11.010
© 2009 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.
