Text version
Use of Long-Acting Antipsychotics for Women with Schizophrenia
In this Quick Take today, we’re going to look at a clinical review about the use of long-acting antipsychotics for women with schizophrenia. This review, which was published in the Therapeutic Advances in Psychopharmacology, caught my interest since the management of women with schizophrenia is shockingly neglected by research and the literature.
The authors basically want to make sure you consider long-acting injectables as an option when treating women with schizophrenia and not just oral antipsychotics across all stages of illness and also during pregnancy and in the postpartum period.
Download PDF and other files
Clinical Differences Between Men and Women with Schizophrenia
If you treat people with schizophrenia in a general psychiatric clinic, you will be immediately familiar with clinical differences between men and women with schizophrenia. The typical female patient with schizophrenia is going to develop schizophrenia later in life, say in their late 20s or even early 30s, often after they have started a family, and after they have finished their education.
Typically, they also show fewer negative or cognitive symptoms, so their psychosocial function is better. Now, this contrasts with the typical male patient who develops schizophrenia at the end of high school or the beginning of college with usually noticeable negative symptoms and some cognitive decline which may prevent them from finishing their education or start a family.
Second Peak of Onset in Women and the Estrogen Protection Hypothesis
There’s a second difference that is interesting and that is that women have a second peak of onset of schizophrenia in their late 40s or 50s which has been attributed to hormonal changes during their menopausal years, specifically a drop in estrogen which is considered protective with regard to developing schizophrenia. That is called the estrogen protection hypothesis, which may be in part responsible for better outcomes in female patients with schizophrenia such as:
- The later onset in general, the first peak
- Fewer negative symptoms
Unfortunately, hormonal treatments for women who develop schizophrenia is understudied and anything but routine clinically despite a good biological rationale why certain treatments may be helpful, like the use of selective estrogen receptor modulators such as raloxifene. But this is a discussion for another day.
Download PDF and other files
Three Clinical Points About Long-Acting Injectables for Women
Let me now give you three clinical points about long-acting injectables for women that I extracted from this review.
#1. Women may be good candidates for long-acting injectables, particularly during pregnancy and immediately after pregnancy during the postpartum period, which are high-risk periods for a psychotic relapse.
These are times of stress, irregular routines, sleep deprivation, during which taking oral medications regularly may be even more challenging than at other times in people’s lives.
Drug levels can change quite a bit during pregnancy and therapeutic drug monitoring, particularly during the third trimester, may be useful.
So while long-acting injectables may be good to protect against relapse during pregnancy and postpartum, there may be two situations where you may want to avoid long-acting injectables according to the review:
- Women at risk of preterm birth as infants may be exposed to high antipsychotic blood levels
- Plan to strictly breastfeed to avoid interfering with known prolactin elevation in lactation
Partial agonist antipsychotics like aripiprazole in particular can lower prolactin and would specifically not be a good choice. Those are situations where you may want to keep your treatment options broader and more flexible, hence avoiding long-acting injectables.
Please note, I did not say avoiding antipsychotics. That is a very tough individual decision with certain clear risks that need to be discussed with your patient.
Clear risk, meaning risk of relapse compared to some risks to the developing fetus.
#2. One consideration that I had not fully appreciated for the use of long-acting injectables in women is using them in those women who already have children and where a psychotic relapse may come at a high price: losing custody over children.
This may be a justified state intervention, but there may also be stigma and prejudice at play in the sense that women with schizophrenia often still are categorically viewed as unfit to be mothers, something that is simply not true at least based on several mothers with schizophrenia that I know and treat.
A long-acting injectable may be a good insurance against relapse for such families so that this issue never gets raised.
#3. Since menopause is associated with a poor response to antipsychotics in women, by default menopause in women, using antipsychotics with less effect on estrogen may be better in later-onset cases.
With long-acting injectables, that really leaves you with aripiprazole as the other widely available long-acting injectables, first-generation antipsychotics and risperidone or paliperidone, all increase prolactin and lead to secondary hypoestrogenemia as a result.
Olanzapine which is available in some countries as a long-acting would also be a good choice in that regard since any prolactin elevation usually happens only at the beginning of treatment.
Clinical Bottom Line
Long-acting injectables are good treatment options for female patients with schizophrenia, including during pregnancy and postpartum, and not just for your typical male patient with poor adherence.
You need to pay particular attention to the hormonal status, particularly estrogen and prolactin.
Partial agonist antipsychotics like aripiprazole are probably better tolerated in general and possibly even more effective in women compared to those antipsychotics that increase prolactin and secondarily reduce estrogen.
Download PDF and other files
Abstract
Long-acting antipsychotic treatments: focus on women with schizophrenia
Sofia Brissos, M.D. & Vicent Balanzá-Martínez. M.D.
Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients’ personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient’s age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.
Keywords: breastfeeding; contraception; long-acting injectable antipsychotics; menopause; postpartum; pregnancy; schizophrenia; sex.
Reference
Brissos, S. M.D., Balanzá-Martínez, V. M.D. (2024). Long-acting antipsychotic treatments: focus on women with schizophrenia. Therapeutic Advances in Psychopharmacology. 31;14:20451253241263715.
