With increased diagnosis and treatment options for psychological disorders, weight gain has become an significant problem.
Many of the approved psychotropic drugs increase body weight and have the potential to cause obesity.
There are increased incidents of metabolic disorders like diabetes, hypercholesterolemia and hypertension in the psychiatric patients group and these are associated to the use of psychotropics.
– BMI ≥ 35 or 40 kg/m2 -> major obesity
– BMI ≥ 35 kg/m2 and health problems associated with obesity, or ≥40–44.9 kg/m2 -> morbid obesity
– BMI ≥ 45 or 50 kg/m2 -> super obesity
3. Mood Stabilizers
4. Effect Mechanism
5. What is to be done?
That antipsychotics lead to weight gain has been known ever since they entered clinical practice.
Although almost all antipsychotics lead to weight gain, low potency phenothiazines and clozapine are particularly in the foreground.
The amount of weight gain varies from drug to drug but second generation antipsychotics in particular lead to significant weight gain.
Second generation antipsychotics
Is the group where the highest weight gain is observed.
According to wide-ranging literature reviews the average increase in body weight is as follows:
– Olanzapine -> 2.3 kg/month,
– Quetiapine -> 1.8 kg/month,
– Clozapine -> 1.7 kg/month,
– Risperidone -> 1.0 kg/month,
– Ziprasidone -> 0.8 kg/month.
No side effects in the short and long-term were reported on the antipsychotic drug Paliperidone which was approved in 2006.
A short-term trial with Aripiprazole showed an average weight increase of 0.5-0.9 kg compared to the placebo.
– Clozapine, olanzapine, risperidone and quetiapine are considered substantially associated with weight increase,
– whereas paliperidone, ziprasidone, aripiprazole, asenapine, and lurasidone are found to be relatively neutral.
Compared to other drugs weight gain on antidepressants (AD) is a more chronic process.
Obesity associated with AD’s is more common because they are prescribed more often than the other drugs.
As second generation antipsychotics are in the foreground with regard to obesity, studies conducted on AD’s are relatively few.
However, a weight gain of 1-3 kg in 10-20 % of the total population due to antidepressants is a bigger problem than a 2-10 kg weight gain in the schizophrenic population which is considered to be 1% of the total population.
Compared to other agents, AD’s side effect of weight gain was reported more frequently in Tricyclic AD’s and Monamine Oxidase Inhibitors.
The weight gain effect can be summarized as follows: «TSA > MAOI > Mirtazapine > SSRI > others».
Tricyclic Antidepressants (TSA)
Users experienced an average weight gain of 3-4 kg. 13.3% of the patients gained more than 10% of their initial weight.
An average weight increase of 2 kg was observed.
No weight gain was recorded in patients over the age of 60 and in children.
Monoamine Oxidase Inhibitors (MAOI)
Cause less weight gain than the tricyclic antidepressants.
According to a literature review it is established that amongst the MAOI, Phenelzine has the biggest tendency to lead to weight gain.
Weight gain with isocarboxazid and transdermal selegiline is rare.
Selective Serotonin Reuptake Inhibitors
Are the most commonly prescribed antidepressants.
Although SSRI’s initial effect is weight loss, after the first year of treatment a general weight gain has been reported.
Amongst the SSRI’s Paroxetine causes the most weight gain.
There is controversial data on fluoxetine. Although initially anorexic effects are seen, there is also data that supports that this effect is temporary and ultimately there is a weight increase compared to the patient’s initial weight.
Citalopram can lead to a weight gain of 1-1.5 kg in a year.
No weight gain is reported with fluvoxamine or sertraline.
With regard to its obesity causing effect, mirtazapine falls between the SSRI’s and TSA’s.
the weight gain and metabolic effects of mirtazapini in clinical practice are considered to resemble those of second generation antipsychotics.
There are studies that show that in time trazodone leads to a weight gain of 0.5-1.1 kg.
Amongst modern agents bupropion is the only one that causes weight loss.
An average weight loss of 3–4.4 kg is reported in users.
Like with antipsychotics and antidepressants, weight gain and obesity are also a common side effect of mood stabilizers.
Amongst mood stabilizing agents, lithium is in the forefront with regard to its weight increasing effect.
In a long-term cohort study it was reported that 74% of patients undergoing lithium treatment have gained weight.
21% of these gained 10 kg or more weight whilst 2% gained 20 kg or more weight.
Other Mood Stabilizers
It is known that it leads to more weight gain than other anticonvulsants.
In 8% – %9 of users an average weight gain of 8-14 kg was seen.
Although studies are limited, a weight increase of up to 15 kg was reported.
Its effect on weight is believed to be neutral. Studies show that it has led to approximately 2 kg weight loss and to 0.6 kg weight gain.
The pharmaco-dynamic effect profile of psychotropes is fairly wide and they can lead to weight gain by interacting with multiple neurotransmitters, receptors and neural networks.
In conclusion, these effects are brought by increasing the appetite (increased intake of calories) and/or by slowing down the metabolism (less calories burned off).
Drug based sedation and reduced physical activity are also to blame.
Serotonin 5-hidroxitryptamine 2C (5-HT2C) Receptors
They play a role in regulating appetite.
Animal studies show that when these receptors are active it results in reduced food intake by the animal. Rats without these receptors have been reported to be obese.
It is thought that atypical antipsychotics and mirtazapine block this receptor thereby leading to increased food and calorie intake.
Beta-3 adrenergic receptors
They are present in the adipose tissue and with the presence of norepinephrine stimulation play a role in turning fat into energy.
Although their full effect is not know, drugs like TSA which have a close affinity to this receptor lead to more weight gain than the SSRI’s.
Although its definite effect is not known, psychotropes that block this receptor lead to more weight gain.
The blockage of anticholinergic areas leads to an increase in appetite.
It is known that sigma-opioid receptors play a role in the effect mechanism of clozapin.
Ideally, a diet and exercise plan should be developed for the patient before the onset of weight gain.
Alongside with diet and exercise, the patient’s eating habits should be changed with the help of behavior regulating techniques and desired dietary habits should be encouraged.
Behavior regulation alone can lead to a weight loss of 0.5-0.7 kg per week.
If all of these fail or if the patient shows limited cooperation it would be appropriate to commence the patient on anti-obesity drugs.
In the public in general and in patients with psychological disorders in particular the prevalence for obesity is steadily increasing.
Almost all of the antipsychotics, mood stabilizers and antidepressants have an effect on the person’s weight.
It is known that few psychotrope drugs have a weight reducing effect.
In addition to their metabolic effects, weight increase can also affect the patient’s drug compliance and can lead to a flare-up of the symptoms.