1 Department of Psychiatry, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan.
Received: 03/18/2017 – Accepted: 03/28/2017
Address for correspondence: Lee-Hou Tsai. E-mail: [email protected]
Tsai LH / Arch Clin Psychiatry. 2017;44(4):111-2
Antipsychotic-induced1 amenorrhea is a serious concern among premenopausal women suffering from mental disorders. Among many women, menstruation is a symbol of femininity that indicates the ability to become pregnant naturally, or is a basis to determine if they are menopausal2. Some patients believe the lack of menstruation signifies menopause and contributes to emotional instability or aggravation of their mental disorder. Patients with amenorrhea often seek help from gynecologists to induce menstruation. Peuskens et al.3 reported that amenorrhea occurred in 22-50% of women treated with antipsychotics. The prevalence of menstrual irregularities and amenorrhea is considered to be 15-97% in women receiving therapy for a psychotic disorder4. It is also common for patients to discontinue antipsychotics due to amenorrhea, which in turn triggers relapses.
I will discuss two cases here: a patient with schizoaffective disorder and another with bipolar I, manic episodes with psychotic features. Both patients achieved full remission of psychotic symptoms, but wanted to switch medications due to lack of menstruation and weight gain. Both patients were middle-aged women in their 40s, with multiple past records of discontinuing their medication that triggered relapses and led to hospitalization. Therefore, I prescribed aripiprazole to facilitate a gradual process of switching medications. Table 1 summarizes the history of past medications, medication switching process, and results of therapy for the two patients. Notably, amenorrhea does not only occur among patients with hyperprolactinemia, but also among premenopausal patients with normal blood prolactin levels, even when using multi-acting receptor targeted antipsychotics (MARTAs), which have an extremely low probability of causing amenorrhea.
Among antipsychotics, hyperprolactinemia is most commonly induced by sulpiride, amisulpride, risperidone, and paliperidone. Paparrigopoulos et al. found that the prevalence rate of hyperprolactinemia induced by amisulpride was 100%, and this was observed more in women than in men5. The prevalence of menstrual side effects such as amenorrhea in patients on risperidone is reported to be 1-10%6. In addition, serotonin-dopamine antagonists (SDAs) are more likely to induce hyperprolactinemia than MARTAs. Psychiatrists thus often use MARTAs, such as olanzapine and clozapine1, to treat female psychotic patients with amenorrhea. However, it has been reported that even olanzapine may lead to hyperprolactinemia7.
Aripiprazole is regarded as a second- or third-generation antipsychotic, mainly because it provides a control mechanism for the dopamine “see-saw”. It reduces the dopaminergic neuron activity in brain regions with dopamine hyperactivity, while increasing the dopaminergic neuron activity in regions with hypoactivity, thereby reducing the number of side effects; regarding reduced side effects, the resolution of hyperprolactinemia has attracted the most attention. Aripiprazole can be used to resolve hyperprolactinemia induced by risperidone8, amisulpride, and ziprasidone9. However, the use of aripiprazole to resolve MARTA-induced amenorrhea has rarely been reported, especially in amenorrhea without hyperprolactinemia. Some may believe that since aripiprazole can reduce amenorrhea, we should attempt to use it in the early stages of disease onset in women. It should be noted that in Case 2, aripiprazole was used during the early stages of disease onset. However, due to its slow antimanic effect, it was combined with zotepine after four weeks, and was only completely replaced by zotepine (100 mg/d) after eight weeks, followed by a switch to aripiprazole after the unexpected occurrence of amenorrhea. In both cases, full D2 antagonists were used initially for rapid therapeutic effect until full remission of the mental disorder, and then were successfully replaced by aripiprazole completely over one to two months. This was a viable therapeutic strategy.
In conclusion, when using antipsychotics among premenopausal women, we should consider the possibility of self-discontinuation of medications due to amenorrhea. Hence, after achieving rapid symptom alleviation using non-aripiprazole antipsychotics, the patient should be switched to aripiprazole, which prevents amenorrhea and may also achieve weight loss. Further clinical studies are needed to explore possible solutions to amenorrhea induced by antipsychotics. Figure 1 summarizes the clinical algorithm used when patients are suspected of antipsychotic-induced amenorrhea7.
- de Azevedo Silveira AS, Loureiro Vasconcelos Rocha DM, de Faissol Attux CR, Daltio CS, da Silva LA, Elkis H, et al. Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in Sao Paulo, Brazil. Arch Clin Psychiatry. 2015;42(6):165-70.
- Seeman MV. Antipsychotic-induced amenorrhea. J Ment Health. 2011;20(5):484-91.
- Peuskens J, Sienaert P, de Hert M. Sexual dysfunction: the unspoken side effect of antipsychotics. Eur Psychiatry. 1998;13:23-30.
- Bargiota SI, Bonotis KS, Messinis IE, Angelopoulos NV. The effects of antipsychotics on prolactin levels and women’s menstruation. Schizophr Res Treatment. 2013;2013:502697.
- Paparrigopoulos T, Liappas J, Tzavellas E, Mourikis I, Soldatos C. Amisulpride-induced hyperprolactinemia is reversible following discontinuation. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:92-6.
- Madhusoodanan S, Parida S, Jimenez C. Hyperprolactinemia associated with psychotropics – a review. Hum Psychopharmacol. 2010;25:281-97.
- Torre DL, Falorni A. Pharmacological causes of hyperprolactinemia. Ther Clin Risk Manag. 2007;3:929-51.
- Kelly DL, Wehring HJ, Earl AK. Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic ELevated prolactin). BMC Psychiatry. 2013;13:214.
- Letter to the Editor, Aripiprazole resolves amisulpride and ziprasidone-induced hyperprolactinemia. Psychiatry Clin Neurosci. 2008;62:624.