Psychotropic Meds Increase Risk for Physical Disease

Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorderWorld Psychiatry. 2015 Jun – PMCID: PMC4471960

This is the category of non-opioid medications the CDC recommends for pain over opioids, which are much safer for the vast majority (95%) of pain patients who do not get addicted.

People with severe mental illness have a considerably shorter lifespan than the general population.

This excess mortality is mainly due to physical illness.

Next to mental illness-related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality 

We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people with schizophrenia, depression and bipolar disorder.

Updating and expanding our prior systematic review published in this journal, we searched MEDLINE (November 2009 – November 2014), combining the MeSH terms of major physical disease categories (and/or relevant diseases within these categories) with schizophrenia, major depressive disorder and bipolar disorder, and the three major psychotropic classes which received regulatory approval for these disorders, i.e., antipsychotics, antidepressants and mood stabilizers.

Antipsychotics, and to a more restricted degree antidepressants and mood stabilizers, are associated with an increased risk for several physical diseases, including

  1. obesity,
  2. dyslipidemia,
  3. diabetes mellitus,
  4. thyroid disorders,
  5. hyponatremia;
  6. cardiovascular disease,
  7. respiratory tract disease,
  8. gastrointestinal disease,
  9. haematological disease,
  10. musculoskeletal disease
  11. renal diseases, as well as
  12. movement and seizure disorders

Higher dosages, polypharmacy, and treatment of vulnerable (e.g., old or young) individuals are associated with greater absolute (elderly) and relative (youth) risk for most of these physical diseases.

To what degree medication-specific and patient-specific risk factors interact, and how adverse outcomes can be minimized, allowing patients to derive maximum benefits from these medications, requires adequate clinical attention and further research.

Below, I’ve picked out some details from this long article regarding the effects of mood stabilizers and antidepressants because the CDC recommends those for pain.


Weight gain is greatest with the second-generation antipsychotics (SGAs) clozapine and olanzapine, while quetiapine, risperidone, paliperidone and iloperidone have an intermediate risk. Aripiprazole, amisulpride, ziprasidone, asenapine and lurasidone have less or little effect on body weight.

Generally, weight gain with antipsychotics is rapid during the first few weeks, slows gradually, and often reaches a plateau within one year.

Results indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic abnormalities, as initial rapid weight gain is a good indicator for long-term weight gain and obesity.

Antidepressants, such as amitriptyline and mirtazapine, and mood stabilizers, such as lithium and valproate, have also been associated with weight gain.


Antipsychotics have been associated with lipid abnormalities to relevant degrees. Adverse effects on triglycerides and cholesterol occur early and may even precede weight gain, pointing to weight-independent, molecular effects in addition to weight-related ones

Diabetes mellitus

An association, albeit of uncertain magnitude, seems to exist between antipsychotics and type 2 diabetes mellitus (DM), affecting about 12% of people receiving these medications

The majority of studies suggest that metabolic abnormalities accumulate rapidly after the initiation of treatment

Antipsychotics may induce DM independent of weight gain and adiposity.

These medications appear to contribute to DM both indirectly, by inducing weight gain, and directly, by promoting insulin resistance

certain mood stabilizers, especially valproate, have been associated with an elevated risk for the development of insulin resistance.

Hypothyroidism and hyperparathyroidism

Hypothyroidism is a common adverse effect of lithium, warranting continued monitoring.

A recent systematic review concluded that, compared to placebo, lithium is associated with increased thyroid stimulating hormone (TSH) levels and clinical hypothyroidism.

Syndrome of inappropriate antidiuretic hormone secretion and hyponatremia

Antidepressants, especially SSRIs, have been associated with the syndrome of inappropriate antidiuretic hormone secretion and with hyponatremia

Based on the above, electrolytes should be checked in patients on antipsychotics, antidepressants and/or mood stabilizers with otherwise unexplained physical or mental state deterioration.


Among antidepressants, venlafaxine is the one most frequently associated with increase in blood pressure, while mirtazapine has been found to be associated with hypertension less than tricyclic antidepressants. Generally, mood stabilizers do not affect blood pressure, unless chronic renal failure induced by lithium affects volume distribution

Coronary heart disease and stroke

The potential cardiovascular effects of tricyclic antidepressants are well known. They can cause orthostatic hypotension, slowed cardiac conduction, and increased heart rate, and are therefore best avoided in patients with pre-existing cardiovascular disease.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are associated with a small, but increased incidence of cardiovascular adverse events (hypertension, tachycardia and orthostatic hypotension)

Liver diseases

The antidepressants with the highest risk of hepatotoxicity include iproniazid, nefazodone, phenelzine, venlafaxine, imipramine, amitriptyline, duloxetine, bupropion, trazodone, tianeptine and agomelatine.

Those with the least potential include citalopram, escitalopram, paroxetine and fluvoxamine.

Monitoring of liver function tests and immediate discontinuation upon emergence of abnormal laboratory findings or signs/symptoms of liver dysfunction are crucial, since most cases of hepatic damage are reversible when detected early.

While every aspect of opioid medication is monitored and CONTROLLED, I don’t believe many patients on antidepressants are monitored for liver function.

Among mood stabilizers, carbamazepine and valproate have been associated with liver dysfunction and should be avoided in patients with pre-existing liver disease.


Longitudinal, cross-sectional and prospective cohort studies, as well as meta-analyses, suggest that antidepressants, particularly SSRIs, at therapeutic doses are associated with decreased BMD and increased fracture risk, especially in older adults.

The increase in risk is highest during the early stages of treatment, with a dramatic increase after initiation, reaching a peak within one month for tricyclics and eight months for SSRIs, decreasing towards baseline following discontinuation

For SSRIs and tricyclic antidepressants, a growing excess risk of fractures has been reported with increasing dose


This review summarized recent evidence for the effect of antipsychotics, antidepressants and mood stabilizers on physical health/illness in patients with schizophrenia, major depression and bipolar disorder.

In general, adverse effects on physical health are greatest with antipsychotics, followed by mood stabilizers, tricyclic antidepressants and newer antidepressants. However, effects vary greatly among individual agents, and interactions with underlying host factors are relevant.

Higher dosages, polypharmacy, and the treatment of vulnerable (e.g., old or young) people seems to be associated with a greater effect on most physical diseases.

Furthermore, clozapine, antidepressants, and lithium, as well as antiepileptics, are associated with reduced mortality from suicide.

Thus, the potential risks of antipsychotics, antidepressants and mood stabilizers need to be weighed against the risk of the psychiatric disorders for which they are used and the lasting potential benefits that these medications can produce.

But if these medications are not used for mood disorders or mental illness, but for pain, are the risks still worth it?

Nevertheless, greater attention to the possible impact of psychotropic medications on the physical health of people with SMI can aid clinicians in selecting appropriate treatments for individual patients whose medication-independent risk factors for specific disorders require special consideration.

Moreover, knowledge about specific medication effects can help implementing appropriate monitoring and management strategies aimed at improving physical and well as mental health outcomes of these generally disadvantaged populations.

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  1. Pingback: Addiction psych questions forced opioid tapering | EDS and Chronic Pain News & Info

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