Weight Gain Associated With Psychiatric Medications  

Weight Gain Associated With Psychiatric Medications  

  • Weight gain in psychiatric populations is a common clinical challenge.
  • •Overweight is an important risk factor for diabetes and cardiovascular disease (CVD) in people with schizophrenia. Factors driving weight gain and the risk of diabetes include poor lifestyle, effects of antipsychotic treatment, pharmacogenetic differences between individuals, and direct effects of some antipsychotic medications to interfere with insulin secretion.
  • •A normal body mass index (BMI) is considered to be between 18.5 and 24.9, a BMI between 25 and 29.9 is classified as overweight, and a BMI between 30 and 39.9 is classified as obesity. Patients with a BMI above 40 are considered extremely obese. 1
  • •An increase of BMI by 1 kg/m results in an 8.4% increase in risk for the development of diabetes.
  • •Many patients suffering from mental disorders gain significant weight when exposed to psychotropic medications.
  • •There is high a prevalence of metabolic syndrome in patients afflicted with serious mental illnesses, particularly those with schizophrenia.
  • •The risks of metabolic syndrome and obesity have increased following the introduction of second-generation antipsychotics.
  • •Metabolic syndrome consists of following conditions: Abdominal obesity, insulin resistance, dyslipidemia with elevated triglycerides levels and low high-density lipoprotein cholesterol, and hypertension.
  • •In general most strategies result in weight reduction in the range of 2 to 3.5 kg and a drop in BMI of around 1 kg/m 234567

Risk Models & Risk Scores

  • •According to a 2014 review of eight studies, as many as 55% of patients who take modern antipsychotics experience weight gain.
  • •The weight gain is thought to be caused by a disruption of the chemical signals controlling appetite.
  • •Studies have shown that on average antipsychotics cause patients to gain more than 8 pounds in 10 weeks.
  • •With prolonged use, antipsychotics are associated with weight gain to varying degrees based on a specific medication. The risk of the weight gain can be subdivided into three groups based on a specific antipsychotic therapy:
    • 1.High risk of weight gain: Clozapine and olanzapine.
    • 2.Intermediate risk of weight gain: Quetiapine, risperidone, paliperidone, iloperidone, sertindole, and zotepine.
    • 3.Low risk of weight gain: Aripiprazole, amisulpride, ziprasidone, asenapine, lurasidone, and most high- to medium-potency first-generation antipsychotics.
  • •Tricyclic antidepressants have been shown to increase appetite and carbohydrate cravings.
  • •Risperidone has a larger weight gain effect than lithium, divalproex sodium, and pimozide.
  • •Severe mental illness is associated with a poor diet and lack of exercise, which are major contributors to weight gain. 1234 67891011

Treatment

Approach to Treatment

  • •BMI should be used to monitor whether a patient is becoming overweight or obese. This requires frequent measurement of weight during the early stages of treatment: ideally weekly for the first 4 to 6 weeks and then every 2 to 4 weeks up to 12 weeks; as a minimum, once every 4 weeks for the first 12 weeks of treatment. Weight and BMI should then be assessed at 6 months and at least annually thereafter unless the clinical situation demands more frequent assessment.
  • •Recommended interventions for overweight and obesity include following three strategies: (1) lifestyle interventions, (2) antipsychotic switching, and (3) adjunctive use of aripiprazole or metformin.
    • 1.Aripiprazole may be of benefit in psychotic patients treated with clozapine or olanzapine, and metformin may be of benefit in patients treated with some antipsychotic medications.
    • 2.Adjunctive use of these drugs is rarely considered in the treatment of most psychiatric illnesses.
  • •Lifestyle interventions are recommended as they have a positive effect in the majority of patients. Lifestyle interventions should always be part of the first-line approach. Lifestyle interventions should be continued in addition to any additional intervention.
  • •When a patient is treated with antipsychotics over a short period of time, weight gain may be minimal and reversible once a drug is discontinued.
  • •Nonpharmacologic lifestyle interventions include diet and exercise, cognitive behavioral therapy, and educational psychotherapy.
  • •Pharmacologic intervention, including switching of medications, should be considered only if nonpharmacologic lifestyle intervention did not result in significant success in weight loss.
  • •Medications that appear to carry the lowest propensity for weight gain: Haloperidol, ziprasidone, lurasidone, aripiprazole, amisulpride, and asenapine.
  • •The risks associated with long-term weight gain must be balanced with the risks associated with a potential exacerbation or recurrence of the underlying psychiatric disorder.
    • 1.Given the complexity of bipolar disorder and its management, a switch of mood stabilizer would best be done by a psychiatrist.
    • 2.Similarly, patients whose psychiatric disorder poses a significant risk of harm to self or others should be referred to a psychiatrist for evaluation and management. 1234 7891011

First-Line Treatment

  • •Switching from a high-risk antipsychotic to a low-risk antipsychotic usually mitigates or reverses weight gain. For second-generation antidepressants, there may be modest weight gain with mirtazapine and paroxetine and modest weight loss with bupropion. Other second-generation antidepressants are weight neutral, but individual variations can occur.
  • •If significant change in weight occurs, switching to or adding a low-risk second-generation antidepressant should be considered.
  • •Selective serotonin reuptake inhibitors (SSRIs) (other than paroxetine) and serotonin and norepinephrine reuptake inhibitors (SNRIs) generally do not cause significant weight gain and may lead to improvements in weight status over the short term, but not long term.
  • •Among the mood stabilizers, such as lithium, valproate, carbamazepine, lamotrigine, oxcarbazepine, and most second-generation antipsychotics, the risk of weight gain is high with second-generation antipsychotics, lithium, and valproate, and low with carbamazepine, lamotrigine, and oxcarbazepine. Given the complexity of bipolar disorder and its management, a switch of a mood stabilizer would be best done by a psychiatrist.
  • •Among sleep aids, benzodiazepines, nonbenzodiazepines, melatonergic hypnotics, doxepin, and trazodone are weight neutral. Diphenhydramine may cause weight gain and can be switched to a weight-neutral hypnotic if needed.
  • •Switching must be evidence-based and take into account status of the condition being treated, efficacy, side-effect profile, potential drug-drug interactions, required laboratory monitoring, and cost of the drug(s) being considered, as well as the patient’s pregnancy status or plan. Given the complexity of bipolar disorder and its management, a switch of mood stabilizer would best be done by a psychiatrist.
  • •Switching from olanzapine or risperidone to ziprasidone, but not from first-generation antipsychotics to risperidone, is beneficial for both weight and metabolic measurements.
  • •Switching from olanzapine to aripiprazole may be worthwhile, with more limited data supporting switches from quetiapine and risperidone to aripiprazole, olanzapine to quetiapine, and olanzapine to lurasidone.
  • •The addition of aripiprazole to clozapine or olanzapine appears to be an effective strategy likely to result in a mean difference of weight loss of around 2 kg (based on the prior studies). 1234 7891011

Pharmacologic Therapy

  • •The weight-protective effects of metformin and topiramate were studied in combination with antipsychotic medications. Addition of these agents shows less weight gain.
  • •The drug reboxetine (4 mg daily for 6 weeks) appears effective for weight prevention, and topiramate (100 to 200 mg daily for 12 weeks) is useful for both prevention and for established weight gain.
  • •Prescribing of SSRIs and SNRIs may be associated with improvements in weight status.
  • Adjunctive aripiprazole. Adjunctive aripiprazole is recommended as a possible intervention for weight gain associated with clozapine and olanzapine.
  • Adjunctive metformin. Metformin should be considered as an adjunct to attenuate or reduce weight gain following antipsychotic medication.
    • 1.Metformin leads to a modest reduction in weight over the short and long term but is less effective than intensive lifestyle intervention.
    • 2.In people taking antipsychotic medications, short-term trials have shown that metformin reduces weight, compared with placebo, by approximately 3 kg.
    • 3.There are some risks attached to metformin that require appropriate monitoring (renal function and vitamin B 12 ).
    • 4.These data suggested that metformin can reverse existing antipsychotic-induced weight gain, with a difference from the effects of placebo treatment of approximately 3 kg. 1234 7891011

Nonpharmacologic & Supportive Care

  • •Lifestyle treatment includes cognitive behavioral therapy and educational psychotherapy, such as cognitive/behavioral group intervention.
    • 1.Cognitive/behavioral interventions provide strategies for adhering to diet and exercise.
    • 2.Lifestyle modifications have proven to be valuable for weight management.
    • 3.On average, these interventions will reduce existing weight by approximately 3 kg more, and BMI by approximately 1 kg/m more, than the control treatment.
    • 4.This intervention group consisted of weekly sessions that centered on various strategies, such as goal setting, discussions on barriers to change, and plans to increase physical activity.
    • 5.It is helpful when participants in the intervention also keep a food and activity journal that is submitted at each weekly session and analyzed.
    • 6.There is no clear evidence regarding the optimal duration of engagement with such interventions. 1234 7891011

Special Considerations

Childhood & Adolescence

  • •Children and adolescents are known to be at a higher risk for weight gain associated with antipsychotic treatment.
  • •Based on several studies, antipsychotic-induced weight gain is very rapid in pediatric patients.
  • •Children and adolescents between the ages of 4 and 18 who were treated with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks showed an average weight gain between 4.4 and 8.5 kg depending on the agent (highest gain was in olanzapine patients, lowest gain in aripiprazole patients).
  • •The weight gain could be both psychological and physiologic and manifest to a greater degree in children.
  • •Thus it is important to assess individual, familial, and contextual variables specific to weight gain in order to prioritize treatment objectives. 1 9

Pregnancy

  • •Weight gain, commonly associated with use of antipsychotic medication, can pose additional risks to women who are pregnant and may result in negative health consequences for these mothers and their infants.
  • •Weight gain and increased BMI in the mother increases the risk of gestational diabetes mellitus, preeclampsia, and cesarean delivery, and in the fetus increases risk of stillbirth and neonatal death. 1

Follow-Up

Monitoring

  • •Monitor weight and metabolic parameters closely throughout the course of treatment.
  • •BMI should be used to monitor whether an individual is becoming overweight or obese.
  • •This requires frequent measurement of weight during the early stages of treatment: ideally weekly for the first 4 to 6 weeks and then every 2 to 4 weeks up to 12 weeks; but, as a minimum, once every 4 weeks for the first 12 weeks of treatment.
  • •Weight and BMI should then be assessed at 6 months and at least annually thereafter, unless the clinical situation demands more frequent assessment. 2345

Prognosis

  • •Weight gain and the development of obesity are important risk factors for diabetes and CVD, but are a common side effect of treatment with psychiatric medications. It is thus essential that proper arrangements for monitoring weight are in place for all those in whom treatment with these agents is indicated, that systems are in place to recognize those individuals who are gaining weight at an early stage of treatment, and that members of mental health teams are aware of the options for managing undue weight gain.
  • •On average, these interventions will reduce existing weight by approximately 3 kg more, and BMI by approximately 1 kg/m more, than the control treatment.
  • •In general, most strategies result in weight reduction in the range of 2 to 3.5 kg and a drop in BMI of around 1 kg/m 234

Referral

A meaningful multidisciplinary team approach is important to target all vulnerable areas. Dietitians should be involved to monitor nutritional requirements. Treatment of metabolic conditions such as hyperlipidemia, diabetes, and hypertension should include the expertise of the primary care provider and/or endocrinologist.

Summary

  • •Many patients suffering from mental disorders gain significant weight when exposed to psychotropic medications.
  • •There is a high prevalence of metabolic syndrome in patients afflicted with serious mental illnesses, particularly those with schizophrenia.
  • •Nonpharmacologic lifestyle interventions, such as improvements in diet, exercise, and lifestyle, supplemented with treatments such as cognitive behavioral psychotherapy, should be initiated first and continued even if an additional drug modification is initiated.
  • •Pharmacologic interventions include switching medication to one or more agents associated with a lower propensity for weight gain.
  • •Prescribing of SSRIs and SNRIs may be associated with improvements in weight status.
  • •Clinicians must balance the possible benefit on weight of switching antipsychotic medication against the risks of inducing relapse of core psychotic symptoms.
  • •Adjunctive aripiprazole or metformin should be considered as an adjunct to attenuate or reduce weight gain following antipsychotic medication.
  • •Given the complexity of psychiatric disorders and their management, a medication switch should be considered in the context of a careful analysis of risks and benefits, and is best done in consultation with a psychiatrist.

References

1.Shrivastava A., Johnston M.: Weight-gain in psychiatric treatment: risks, implications, and strategies for prevention and management . Mens Sana Monogr 2010; 8 (1): pp. 53-68.

2.Cooper 1 S., Reynolds G., et al.: BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment . J Psychopharmacol 2016; 30 (8): pp. 717-748.

3.Hasan A., Falkai P., Wobrock T., et al.: World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of schizophrenia, Part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychoticinduced side effects . World J Biol Psychiatry 2013; 14: pp. 2-44.

4.Mukundan A., Faulkner G., Cohn T., et al.: Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems . Cochrane Database Syst Rev 2010; 12: pp. CD006629.

5.Morrato E.H., Newcomer J.W., Kamat S., et al.: Metabolic screening after the American Diabetes Association’s consensus statement on antipsychotic drugs and diabetes . Diabetes Care 2009; 32 (6): pp. 1037-1042.

6.Abosi O., Lopes S., Schmitz S., Fiedorowicz J.: Cardiometabolic effects of psychotropic medications . Horm Mol Biol Clin Investig 2018; 36 (1):

7.Citrome L., Vreeland B.: Schizophrenia, obesity, and antipsychotic medications: what can we do? . Postgrad Med 2008; 120 (2): pp. 18-33.

8.Citrome L., Vreeland B.: Obesity and mental illness . Mod Trends Pharmacopsychiatry 2009; 26: pp. p25-46.

9.Correll C.U., Manu P., Olshanskiy V., Napolitano B., Kane J.M.: Malhotra Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents . J Am Med Assoc 2009; 302 (16): pp. p1765-1773.

10.Bak M., Fransen A., Janssen J., van Os J., Drukker M.: Almost all antipsychotics result in weight gain: a meta-analysis . PloS One 2014; 9 (4): pp. e94112.

11.2015 . Scientific American. Andrea Alfano , July 1 . https://www.scientificamerican.com/article/many-psychiatric-drugs-have-serious-effects-on-body-weight/ .

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