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My cousin by marriage was a catalogue model before the advent of online shopping put most catalogues out of business. She was a size zero, more or less, and her figure the envy of all we considerably chubbier relatives. But a few years ago, we stopped seeing her at family gatherings. She was always gave a reason but none seemed credible until we learned that she hardly ever left home at all. The reason? She was embarrassed to be seen in public. She had gained a hundred-plus pounds on a medication she was taking and felt it destroyed her life as she knew it.
Olanzapine, better known by the brand name Zyprexa, is an effective drug for the treatment of schizophrenia. It is also used to treat generalized anxiety disorder, and some types of bipolar disorder. At some point, I learned that she was taking the drug for a severe case of generalized anxiety, but given the weight she gained as a side effect, this cure may have actually diminished her mental health.
Olanzapine treatment is associated with rapid and significant weight gain; an analysis of the weight gain potential of anti-psychotic medications found that this drug caused the greatest increase in weight. The drug seems to dismantle the brain’s ability to control appetite, and so patients must contend with a seemingly unceasing need to eat. This unwelcome side effect has been reported to start almost immediately: One study found that almost 60% of patients who began this drug therapy experienced a significant increase in appetite during the first four weeks of treatment. The number increased to 80% during the following weeks. Patients’ lipid and cholesterol levels were negatively affected as well: 50 percent showed signs of dyslipidemia by three months. Their ratio of LDL cholesterol (the bad kind) to HDL cholesterol (the good kind) was significantly increased and consequently, their risk of coronary heart disease and stroke increased.
Increased appetite is offered as an explanation of the excessive food intake, but an absence of satiety may be as likely the cause of the overeating. Typically the patient finishes a large meal but does not feel full, despite a stomach that has enough food to decrease the desire to continue eating. Sometimes, only an hour after the earlier meal has been completed, the need to eat arises again. The mental perception of satiety seems to be absent, despite the physical sensation of having eaten enough food. We treated obese patients who had gained weight while on anti-psychotic medication at a weight-loss clinic associated with a Harvard Medical School-affiliated psychiatric hospital. They would tell us that they were unable to stop themselves from eating one meal after the next. Many would also wake up at night needing to eat. One patient described her need to eat as similar to being thirsty and never being able to drink enough water to satisfy her thirst.
The weight gain, sometimes as much as 125 pounds, often exerts a social and psychological toll on a patient. Like my cousin, many stop interacting socially and find it difficult to accept a body image so at odds at the way they looked before being treated. Indeed, patients may face the double stigma of having a mental disorder and morbid obesity. A woman I know who gained almost 90 pounds during treatment for bipolar disorder kept a picture of herself prior to treatment in her wallet. She needed to show people she met that the body she wore now was not really hers.
Recently the FDA approved a drug that may decrease the weight gain. Lybalvi is a combination of two drugs: olanzapine and samidorphan. FDA approval was based on studies monitoring the weight gain of patients during 4 weeks and, subsequently, 24 weeks of treatment. Weight gain of patients given the combination drug was compared with the weight gain of those receiving only olanzapine. Both treatments were effective in treating psychotic symptoms, and markers of metabolic health such as blood glucose and triglyceride levels did not differ between the two groups. However, after 24 weeks, patients on the combination therapy gained 3.2 kg (7 lbs) and those on olanzapine alone gained 5.1 kg (11 lbs). However, another study did not reveal any difference in weight gain between the two treatments: Short-term weight change was found to be statistically similar. These authors suggest that the drug combination may be more effective during prolonged treatment. Lybalvi has been used to treat bipolar disorder but so far there is no information as to whether weight gain is slowed in those patients.
What patients tend to be left with is a situation that is bad—i.e., considerable weight gain—and perhaps not so bad—i.e., less weight gain. The concern over weight gain is far from cosmetic as it is associated with an increased risk of cardiovascular events. Patients often need to be treated for months, even years, and the long-term effects of the new drug combination are not yet known.
One approach may be to determine more precisely how food intake changes with olanzapine treatment: When during the day does the ravaging hunger seem least controllable? Do all patients wake up in the middle of the night to eat? Does the social isolation of someone with schizophrenia exacerbate the eating?
Certainly, as we know well from the pandemic, isolation may cause an increase in food intake, and it may be possible that the absence of any social or work distractions makes it difficult for patients to avoid eating when their stomachs are still full. Are patients eating unhealthy, high-fat foods because they are cheap and require little preparation? Would they gain as much if they were able to follow a food plan with more vegetables and fruit? Are there any foods that might make the patient feel more satisfied after eating, and thus reduce the tendency to eat again within a short period of time? In short, while we are waiting for an anti-psychotic drug that will not cause weight gain, are there interventions that might, at the very least, insure that the patient’s food intake is healthy? Perhaps might there be additional interventions offered to reduce the social factors, such as isolation, that often also lead to excess eating.
Pharmaceutical relief for emotional disorders shouldn't cause distressing weight gain. Perhaps non-judgmental social outreach to reassure is a complementary behavorial approach reminding patients that it's what's on the inside that counts most.
