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What is the clinical response to the occasional presence of psychotic symptoms among patients with eating disorders?
While treating women with psychotic illness, I noticed that many of my patients, in addition to their psychosis, had eating disorders (anorexia and binge eating) and I wondered whether my prescription of antipsychotic drugs was responsible. I knew that these drugs led to increased appetite and weight gain, which could provoke a counter reaction, ie, a drive to be thin.
The neuroscientist and author Erin Hawkes-who was treated for schizophrenia with olanzapine-writes about how her bulimia subsequently intensified:
I was put on olanzapine. Terrible mistake: I was, within two months, 137 pounds of (in my opinion) fat. My purging went wild. . . . Olanzapine gave me a ravenous appetite. . . . Thus, purging became all-important.1
She is not the only person to have made the connection between antipsychotic medication and increased eating disorder symptoms. Olanzapine and clozapine in particular have been implicated in medication- induced bingeing secondary to antipsychotic drug intake.2,3
On the other hand, a 2013 meta-analysis of 8 randomized trials involving olanzapine, risperidone, or amisulpride in eating disorders concluded that, when compared with placebo, these agents did not cause significant body dissatisfaction, nor did they curtail eating.4 Note, however, that the participants in these trials had an eating disorder and were not being treated primarily for psychosis. The doses in the 8 trials were relatively low (eg, 4.2 to 10 mg of olanzapine)-substantially lower than they would have been had the target been psychotic symptoms. Moreover, only 2 of the 8 trials controlled for medication adherence-a particularly significant issue for patients with an eating disorder, who would be strongly tempted to stop treatment if it made them gain weight.
Antipsychotics are sometimes used off label for eating disorders. The reason is because clinicians find it difficult to distinguish the firm belief that one is fat (when that is clearly not the case) from a delusion. The body image disturbance at the heart of anorexia nervosa is a false perception akin to the perceptual disorders found in schizophrenia. Additional psychotic features associated with eating disorders-usually transient-have been attributed to the effects of starvation and electrolyte imbalance.
Mavrogiorgou and colleagues5 report the case of a 37-year-old woman with anorexia who, for 4 years, had acute paranoid-hallucinatory psychosis at the tail end of fasting episodes (when she was most starved). Psychotic symptoms were not in evidence either before or after the fasting periods; this suggests a cause-and-effect relationship between starvation and psychotic decompensation. The authors hypothesize that starvation led to acute hyperactivity of the dopaminergic system, giving rise to a subsequent transient psychosis.
However, despite several potential explanations for the co-occurrence of the conditions, it is possible that eating disorders and psychotic disorders are different phenotypic expressions of a similar genetic predisposition (Figure).
Categorical overlap between eating disorders and psychosis
It is customary for psychiatry to categorize different types of psychiatric illnesses as qualitatively distinct from one another. An early study that used this categorical approach looked at the likelihood of a change in diagnosis over time in persons initially admitted to the hospital with an eating disorder.6 The investigators found that of more than 1000 patients admitted to Danish psychiatric institutions from 1968 to 1986, one-fifth were subsequently readmitted; of those, 6% received a diagnosis of psychosis at the second hospitalization. A later review concluded that a concurrent diagnosis of schizophrenia and anorexia nervosa was rare.7 More recently, Miotto and colleagues8 found no cases of comorbid schizophrenia in more than 100 female patients with DSM-IV eating disorders.
The co-occurrence of the 2 types of disorder may be more prevalent in men. In a study of male veterans with an eating disorder, 28% had a diagnosis of schizophrenia or other psychosis.9 The incidence of psychosis was more than 3 times that of male veterans who did not have an eating disorder, and also more than 3 times that of female veterans with an eating disorder. One potential explanation for these results is differential gender expectation on the part of the diagnostic team. Clinicians tend to be less familiar with eating disorders in males. When they encounter cognitive distortions and food phobias in males, they think of psychotic illness first, while in females they think primarily of eating disorders.
Overall, there seems to be little evidence for the commonly advanced speculation that psychotic illness such as schizophrenia can occur in up to 10% of patients with eating disorders. The incidence of psychotic illness in patients with an eating disorder appears to be approximately that of the population at large, although individual psychotic symptoms-such as occasional paranoid ideation (feeling that others are to blame for troubling events) and alienation (never feeling close to another person)-may be more frequent.8
In a study of eating disorders in a population with previously diagnosed psychosis, GÃ¶testam and colleagues10 found that among 19,000 inpatient Norwegian males with schizophrenia, almost 2% had a diagnosed eating disorder. This is considered a high figure for anorexia nervosa in men but may or may not be a high figure for all eating disorders. Study results differ depending on the sociocultural background of the sample and on whether it consists of service users or community members (there is less of a male to female rate difference in the latter).11,12
Whatever the case, there seems to be a greater overlap between eating disorders and psychotic disorders in males than in females. This overlap seems more evident in care settings for patients with psychosis than in those for patients with eating disorders, which throws suspicion on the role of antipsychotic medication.
Dimensional overlap between eating disorders and psychosis
In contrast to a categorical model of psychiatric disease, a dimensional model acknowledges that psychiatric disorders are inherently heterogeneous and overlapping. This method of classifying psychiatric disorders is becoming more popular because syndromal overlap is more the rule than the exception in the clinic.
Eating disorders and psychotic disorders are both characterized by distorted thoughts, overvalued ideas, depersonalization and derealization phenomena, and delusions. Moreover, auditory hallucinations, considered to be the hallmark of psychosis, can also occur in anorexia nervosa. A basic mistrust of others-a trait that often leads to social isolation, poor therapeutic alliance, and poor treatment adherence-is common to both eating disorders and psychotic disorders. The ability to put oneself in the mindset of the other person (theory of mind) is deficient in both disorders, as are difficulties in shifting sets or being able to pass quickly from one mode of thinking to another.
Genetic overlap between eating disorders and psychosis
A genetic basis exists for most disorders and this, too, can overlap among diagnostic categories. Data from the National Survey of American Life show an association between having a first-degree relative with schizophrenia and the lifetime risk of bulimia, among other disorders.13 Trace and colleagues14 found that dopamine receptor D2 polymorphisms were significantly associated with anorexia nervosa. Data from genome-wide association studies in schizophrenia show the same associations.15 Both disorders have been linked to altered dopamine activity: expressed mainly by hyperactivity in anorexia nervosa and by delusions and hallucinations in psychotic illness.
Comorbidity between eating disorders and psychotic illness is seen more commonly in care services for psychotic disorders than in treatment programs for eating disorders, despite the fact that the self-starvation associated with some types of eating disorder can often result in psychotic symptoms. It is possible, therefore, that the treatment of psychosis (ie, with antipsychotic medication) may, in part, be responsible. The Table presents recommendations intended to minimize the risk of triggering eating disorders when treating patients who present with a psychotic illness.
Antipsychotic doses should be kept as low as possible. Remember that positive symptoms of psychosis, which are targeted by antipsychotic medications, need not always be totally eliminated for patients to enjoy a good quality of life. The treatment target should be function, not symptoms. Attempts to eliminate all psychotic symptoms can induce anorexia nervosa, which is in many ways more dangerous than the original problem, with higher mortality than any other psychiatric disorder.
Dr Seeman is Professor Emerita in the department of psychiatry at the University of Toronto, King’s College Circle, Toronto, Ontario, Canada. She reports no conflicts of interest concerning the subject matter of this article.
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