The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

Abstract

During the postpartum and menopausal periods of women’s lives, there is a well-established and significant drop of circulating estrogens. This may be the reason why both these periods are associated with an increased risk for onset or exacerbation of psychiatric disorders. Whether symptoms are mainly affective or mainly psychotic, these disorders are frequently treated with antipsychotic medications, which calls for an examination of the relationship between hormone replacement and antipsychotic agents at these time periods. The aim of this narrative review is to summarize what is known about the association of hormones and antipsychotics in the postnatal period and at menopause. In the review, we focus on estrogen and oxytocin hormones and include, for the most part, only papers published within the last 10 years. Both estradiol and oxytocin have at various times been implicated in the etiology of postpartum disorders, and estrogens, sometimes combined with progesterone, have been tested as potential treatments for these conditions. The role of estradiol as an adjunct to antipsychotics in the prevention of postpartum relapses is currently controversial. With respect to oxytocin, studies are lacking. Psychosis in menopausal and postmenopausal women has been successfully treated with estrogens and selective estrogen-receptor modulators, mainly raloxifene, in addition to antipsychotics. Some symptoms appear to respond better than others. No oxytocin study has specifically targeted postmenopausal women. Because of feedback mechanisms, there is a theoretical danger of therapy with exogenous hormones interfering with endogenous secretion and disturbing the balance among inter-related hormones. When used with antipsychotics, hormones may also affect the metabolism and, hence, the brain level of specific antipsychotics. This makes treatment with antipsychotics plus hormones complicated. Dose, timing and route of intervention may all prove critical to efficacy. While much remains unknown, this literature review indicates that, within standard dose ranges, the combination of hormones and antipsychotics for postnatal and menopausal women suffering severe mental distress can be beneficial, and is safe.

Polycystic Ovary Syndrome and Psychotic Disorder

“…Compared to untreated psychiatric controls, Galling and colleagues (37) reported an incidence of T2DM three times higher in youth treated with antipsychotics for over three months. Antipsychotic-induced diabetes has been confirmed in animal models; both olanzapine and clozapine have been shown to decrease the plasma level of insulin and to cause hyperglycemia and insulin resistance in rats (16).…”

“…When levels decline, the emergence of psychotic symptoms is facilitated (15). For instance, several literature reviews suggest that, in women with chronic psychotic illness, symptoms are aggravated during the premenstrual period (16), after delivery (17) and at menopause (15).…”

Clozapine Efficacy in a Case of Severe Treatment-Resistant Postpartum Psychosis

“…Women who are already vulnerable as a result of genetics or stressful environmental exposure are susceptible to mental disease in this period and this was attributed to neuro-hormonal factors. 6 The levels of estrogen and oxytocin gradually rise during the pregnancy and drop sharply after delivery, returning to normal within 3 weeks. Considering that the occurrence of psychosis is associated in time with the abrupt decline of the two hormones, an increased sensitivity of dopamine receptors due to the sudden decrease in estrogen levels has been involved.…”

“…Given the putative role of estradiol and oxytocin in the pathophysiology, both estrogens (sometimes associated with progesterone) and oxytocin have been tested as potential treatments for nonpsychotic and psychotic illness in the puerperium, but the results of the clinical studies available so far are inconclusive to sustain their use. 6 …”

“…In this case, the outcome may depend on the antipsychotic agent; olanzapine and clozapine are metabolized by CYP1A2 liver enzyme, which is inhibited by estrogen; co-administration of estrogen will increase the antipsychotic level, while quetiapine is mainly metabolized by CYP3A4, which is induced by estrogens, so the antipsychotic level will decrease. 6 …”