The Importance of Pharmacogenomics: The Need for Varied Mental Health Treatment

Pharmacogenomics deals with pharmacology and genomics, studies the role of the genome in drug response, and analyzes how the genetic makeup of individuals affects their response to drugs. 

For decades, studies were conducted mostly, sometimes exclusively, in male humans and animals. Today, agencies funding research are mandating changes. As we alluded to in a previous post on the potential of psychedelic and other medical fields for treating mental health, learning about the differences in mental health between those who identify as men and women might enhance how we treat them.

Men and women are affected at about the same rate for many conditions, like schizophrenia and bipolar disorder, but there is evidence that some sex differences in the rate of mental health disorders are changing. Certain symptoms are more common in women than in men, and a person’s sex can affect the course of the illness. In countries in the global north, the gap between men and women in the occurrence of substance use is shrinking.

Researchers are only now exploring the various biological and psychosocial factors affecting the mental health of women and men.

How Mental Illness Shows Up in Men and Women 

While depression symptoms are generally the same for men and women, globally, depression is twice as common in women due to gender-specific risk factors: gender-based violence, socio-economic disadvantages, income inequality, low social status and rank, and responsibility for others and the health of their families, including dependent relatives. Postnatal depression affects up to 15% of women after they have given birth.

Symptoms of irritability, sudden anger, increased loss of control, risk-taking and aggression are more common in men. They are also more likely to work more, and use alcohol or drugs to cope with their mental health.

Symptoms of anxiety may be more pronounced in women, but partly because it is more typical of women to express feelings compared to men. Some women may experience mental disorder symptoms such as perinatal depression, premenstrual dysphoric disorder, and perimenopause-related depression during times of hormonal changes.

In the US, anxiety affects women at twice the rate that it affects men, and depression is more common among women. Women’s jobs are more at risk from automation than those of their male counterparts. Though more research is required to explain this biologically, it links anxiety to socioeconomic factors like inequity in education, income, occupation, housing or food insecurity, lack of purpose (particularly at work), bullying, isolation and loneliness, and physical health.

A study of adults living in Spain during the lockdown of COVID-19 (spring 2020) found more women reporting anxiety and depression levels, especially in young women aged 18–35. 

Regarding stress management, men reveal more physiological changes such as blood pressure, and physical diseases such as hypertension, cardiovascular disease and diabetes.

Women have increased stress-induced myocardial ischemia and a higher probability of thrombus, are more affected by social sources of distress, and respond to stressors with psychological diseases. Somatic symptoms (headaches, palpitations) may disguise an anxiety disorder. Fatigue and myalgia may have an underlying diagnosis of depression (Samad Z, et al. J Am Coll Cardiol 2014;64:1669-78).

Women are the largest single group of people affected by gender-based violence and a correspondingly high rate of Post Traumatic Stress Disorder (PTSD) following sexual violence, and abuse is often a factor in their mental health problems.

Both sexes are susceptible to eating disorders, but about two-thirds are women. Trans women are even more likely to struggle with more severe eating disorders.

While more men die by suicide, more women attempt to take their own lives, likely because depression rates are higher in women. According to a 2018 study, nearly 30% of transgender women attempt suicide as adolescents or teenagers. 

However, higher rates of suicide by men occur in minority communities: gay men, war Veterans, men of colour, and those with low incomes, which could be attributed to socioeconomic hardship, unemployment, relationship breakdown, and lack of social support.

Since women have a higher life expectancy than men, they make up two-thirds of people with dementia.

Photo: Engin Akyurt

Differences Reveal the Need for More Pharmacogenomics Research

Evident from the study of adults during COVID lockdown, strategies for public health emergencies must include mental health and its determinants, and take a gender-based approach into account in order to reduce health inequities.

More women than men receive medication for a mental health condition. Women are more frequently overdosed because of smaller volume of distribution, larger free fraction of drug (the portion that exerts a pharmacologic effect), and slower clearance from the body. Women are more sensitive to drugs due to alterations in receptor number and binding and signal transduction pathways.

Pharmacokinetics is the movement of a drug into, through, and out of the body. Pharmacodynamics studies the biochemical, physiological, and molecular effects of drugs on the body. Alterations in these practices result in women taking more medications with increased risk of drug interactions.

Psychiatric drugs that differ for men and women include clozapine, olanzapine, and selective serotonin reuptake inhibitors (SSRIs), and substances such as ethanol, methadone and morphine. Women usually have higher responses to SSRIs than tricyclic antidepressants (whilst the reverse is true for men) and require lower doses of typical antipsychotics to control symptoms than men. Antipsychotic adverse incidents are higher in women (FDA.gov).

In a 12-month, randomized controlled trial of a collaborative care (CC) intervention for anxiety disorders (panic disorder, generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder), women showed clinical improvements that differed significantly from women in usual care, while there were no differences for men compared to usual care. In the intervention group, women attended more sessions of psychotherapy, completed more modules of therapy, expressed more commitment, and viewed psychotherapy as more helpful than men.

A secondary analysis of a double-blind, phase III, randomized controlled trial explored sex differences in treatment outcomes in patients receiving injectable opioids for treatment of long-term opioid-dependence and whether men and women have different perceptions of treatment effectiveness. For both men and women, improved health and quality of life were the most common reasons provided for treatment effectiveness, but women were more specific in the health improvements.

Gender and sex-specific factors can make a difference in implementation of treatment. More research is important, and it’s critical that studies include potential sex and gender differences, and age.

“There is a real need for studies that consider how men and women may have different treatment needs, ranging from medication doses and types to behavioral and psychosocial treatments,” said McLean Hospital’s Dr. R. Kathryn McHugh.

She continued: “Research has not suggested men and women have substantively different treatment response overall.”

A study done in 2014 involving mentally ill emergency department patients concluded that more research must be done on:

  • Gender differences in patients with psychiatric diagnoses in regards to chief complaints, disposition, pharmacological and behavioral interventions, and economic costs
  • Interventions and sex- and gender-specific analyses of specific outcomes such as recidivism rates, decreased post-traumatic stress disorder, and substance use; and 
  • Inclusion of patient preference for and acceptance of sex- and gender-specific screening, intervention, and treatment strategies.

No studies have been done comparing use of psychedelics for mental health treatment in men and women.

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