Other e-weekly topics have addressed issues related to pregnancy, menopause, and birth control with mental health, so this topic will focus on general differences between men and women, on how psychotropic medications are absorbed and metabolized, and on how side effects can differ based on gender.

Clearly, some of these differences are related to hormonal effects. Differences in a woman’s hormones based on her menstrual cycle can affect her absorption, metabolism and response to a particular medication.

In general, women tend to have more side effects than men to psychotropic medications.  Research has shown that women are between 50 and 75 percent more likely to experience side effects to psychotropic medications.  They report more weight gain with second-generation antipsychotic medications and antidepressants than men do. They report more EPS side effects with first generation antipsychotic medications, particularly over the age of 50.

Studies have shown that premenopausal women have slower gastric emptying time compared to men, which can lead to a delay in passage of a medication into the small intestine. This can cause slower absorption, delayed peak levels and shorter peak serum concentration of the medication.

Serum levels of medications tend to be higher in women than men, and there are many possible contributing factors. Contributing factors include: females have lower total blood volumes compared to males; while females tend to have a higher percentage of body fat compared to males, the gradual release of lipophilic medications into the blood stream can affect serum levels of medication; and females have a slower clearance of medication through the liver and kidneys. This finding may help explain why women have more side effects to psychotropic medications than men, so an optimal dose for a male may be on the higher side for a female.

To make things more complicated, some of these variables can vary throughout a woman’s menstrual cycle. Examples are total body water volume and gastric emptying time.

While it would be impossible to monitor all of these details when prescribing psychotropic medication, the goal of this article is to make readers aware of the key physiological differences between males and females when it comes to absorption and metabolism of medication which can have a clinical impact.

ASSESSMENT:
During the assessment, it is important to ask a thorough menstrual history as well as ask if the patient is experiencing other physical symptoms of menopause. The menstrual history should include if her cycle is regular or irregular, the heaviness of the flow, and when she had her last menses. Perimenopause begins when the cycle begins to vary and ends 12 months after the last menses. If it is clinically unclear if a patient is in perimenopause, one can measure FSH and estrogen levels during the early follicular phase to confirm perimenopause. During perimenopause, vasomotor symptoms (VMS) and mood lability may worsen. VMS includes hot flashes and night sweats. Other physical symptoms of menopause include: forgetfulness, insomnia, sexual changes (decreased desire, vaginal atrophy), joint pains, bladder discomfort, breast pain, and headaches. Patients with VMS are more likely to have mood symptoms associated with menopause, which can include: irritability, mood lability, and anxiety. Both the mood changes associated with menopause as well as VMS are linked to dysregulation of monoaminergic neurotransmitter systems caused by fluctuating estrogen levels.

TREATMENT OPTIONS:
Treatment is based on if the patient is in perimenopause and the severity of the mood symptoms. The other factor is the appropriateness of hormone replacement therapy (HRT). While there has been much controversy about HRT since the Women’s Health Initiative study in 2002 showed concerns about possible increased risk of breast cancer and limited cardiac protection of HRT, more recent evaluation of the study results has reduced many of these concerns.

As a result estrogen is the only FDA approved treatment for VMS, and since mood symptoms of menopause are so intimately linked to VMS, theoretically estrogen would be a good treatment for depression linked to menopause as well. If the patient is in perimenopause and HRT is an option, studies have shown that HRT can be helpful for both the mood symptoms of perimenopause as well as VMS, so it can be an appropriate treatment for women presenting with mild-moderate mood symptoms related to perimenopause. If HRT is not an option or if the mood symptoms are more severe, treatment with an antidepressant is an option.

Studies have shown that the selective norepinephrine reuptake inhibitors (venlafaxine, duloxetine) are more helpful for VMS than the serotonin reuptake inhibitors, so if HRT is not an option, one might consider starting with an SNRI to treat both the mood symptoms as well as the VMS. If HRT is an option, one might consider a combination of HRT and an SSRI as an alternative approach. If the patient is not clearly in perimenopause, then treatment should proceed as usual, with the SSRIs being the first like agents for moderate-severe depression. Of course, for all patients, adjunctive supportive or cognitive-behavioral therapy should be strongly considered.