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(PDF) Dramatic weight loss associated with commencing clozapine
BMJ Case Reports 2011; doi:10.1136/bcr.09.2011.4790
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His thyroid function remained normal and his full blood
chemistry proﬁle was normal. There was no evidence of
an emergent psychiatric disorder which may have contrib-
uted to his weight loss, such as obsessionality with weight
reduction and he scored in the subclinical range on the
Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Clozapine 150 mg in the morning and 350 mg at night.
OUTCOME AND FOLLOW-UP
He experienced gradual weight loss following the com-
mencement of clozapine and associated with a concerted
effort to engage in a low calorie diet and exercise regime,
with a reduction in weight from 127 kg to 76 kg (BMI 41.5
) over a period of 3 years. He lost 24 kg
of weight during the ﬁrst year of treatment with clozap-
ine. This was followed by a loss of 27 kg over the next 18
months, representing a 40% loss of weight in total and a
normal BMI of 24.8 kg/m
His weight has been subse-
quently stable at 76 kg over 6 months of follow-up. He has
not developed hypertension since the commencement of
clozapine. He has tolerated clozapine well with no adverse
side effects save for constipation.
He remained physically well. There was no symptoma-
tology consistent with gastrointestinal pathology which
may have caused his weight loss.
He has not been rehospitalised in the 3 years since com-
mencing clozapine whereas prior to clozapine therapy he
was hospitalised on 11 occasions over a 20-year period. He
has experienced a marked symptomatic improvement and
a signiﬁ cant improvement in his psychosocial functioning
and insight. He lives independently and is a keen participant
in group activities such as art and cooking classes. He has
re-established a meaningful relationship with his immedi-
ate family members, from whom he was estranged, who
he now visits on a regular basis. He has sustained a weight
control programme and currently walks approximately 3–4
km at least 5 days per week and attends a local gym twice
weekly, where he engages in 60 min of aerobic exercise on
a treadmill. He also swims on two occasions per week. He
has a much reduced calorie intake and has maintained a
high ﬁbre and low fat/cholesterol diet.
This case study is striking because clozapine use is consist-
ently associated with the greatest degree of weight gain
compared to other antipsychotic medications.
is the most effective antipsychotic medication for patients
with treatment resistant schizophrenia
but its use is lim-
ited by its tolerability proﬁ le including weight gain, meta-
bolic dysregulation and the risk of agranulocytosis. The
cumulative incidence of patients becoming overweight on
clozapine exceeds 50%
with a mean weight gain of 4.45
kg at 10 weeks of treatment,
compared to a mean weight
gain of 4.15 kg for olanzapine and 2.1 kg for risperidone
and with an average weight gain of 11.7 kg over a period
of 8 years of treatment.
The mechanism of weight gain with clozapine is uncer—
tain but a number of different mechanisms of action are
thought to contribute. The afﬁnity of clozapine for the H1
receptor and the 5HT2c receptor is most closely linked
to this increased weight gain, although afﬁnity for D2,
5-HT1A, and a2-receptors may also be involved.
evidence that clozapine interrupts hypothalamic control of
body weight which may be due to antipsychotic induced
leptin resistance in the hypothalamus.
The use of direct participation in exercise group activi-
and direct management of diet in supervised accom-
have shown some success in promoting weight
loss for patients with severe mental illness. These were
two approaches which were utilised in our patient’s case.
There was an improvement in the degree of severity of the
negative symptoms of schizophrenia which he displayed.
This was associated with increased levels of motivation,
improved initiative and an ability to engage more fully in
goal directed physical activity.
Another recent case series reported weight loss following
treatment with clozapine in three patients, with percent-
age loss of body weight of 49%, 21% and 19%,
the authors speculate could be due to genetic variation in
neuroreceptors. A further case series reported weight loss
in ﬁve patients who failed to respond to clozapine treat-
ment. They described a range of weight loss from 4 kg to
13 kg and hypothesised that early weight loss may be an
indicator of a poor clinical response to clozapine in treat-
ment resistant schizophrenia.
It has been reported that
up to 10% of patients on clozapine will develop obsessive-
The development of obsessional-
ity with food or compulsive exercise or dieting was not
present in this case to explain the dramatic weight loss.
Rather it appears that the clinical improvement in symp-
toms and functioning provided by the switch to clozap-
ine facilitated a recovery which, among other quality of
life improvements, resulted in the full reversal of weight
increase built up over many previous years of psychotic
illness and its treatment.
▶Clozapine is the most effective antipsychotic
medication for treatment resistant schizophrenia but
its use is limited by its tolerability proﬁ le such as
weight gain and metabolic dysregulation.
Risk factors for cardiovascular disease (CVD) such
as obesity, smoking, diabetes, hypertension and
dyslipidaemia are more common in patients with
schizophrenia than in the general population and the
use of clozapine can induce weight gain and worsen
CVD risk factors.
This case demonstrates that despite the risks of
substantial weight gain and dyslipidaemia which are
characteristically experienced by many patients on this
treatment, the signiﬁ cant symptomatic and functional
improvement achieved with clozapine therapy can in
fact completely reverse these risks.
The patient had a sustained response to clozapine
therapy with a signiﬁ cant reduction in psychotic
symptoms which was associated with improved
physical health and quality of life.
Competing interests None.
Patient consent Obtained.
A 26-year-old man with a history of longstanding treatment-resistant schizophrenia gained a substantial amount of weight while being treated with high-dose combination antipsychotic therapy with olanzapine and amisulpride. The patient was switched to combination therapy with olanzapine and aripiprazole to reverse a drug-induced hyperprolactinemia. The patient subsequently lost over 37 lb in weight over a period of 4 months despite no measurable changes in his dietary caloric intake or in his level of physical activity and without any identifiable medical cause on physical investigation.
The timing of the weight loss following the addition of aripiprazole and the exclusion of a medical cause point toward a causal relationship between the change in the patient’s medication and the dramatic change in his body weight. We propose that, in a subgroup of patients, the addition of aripiprazole to their antipsychotic regime (without stopping the offending antipsychotic in terms of weight gain) can result in very significant weight loss and even the reversal of antipsychotic-induced weight gain.
BOLAND and CHHABRA: West London Mental Health NHS Trust, London, UK
Patient Consent Statement: Following a formal assessment of the patient, it was decided that he did not have the capacity to consent to the publication of this report. This is in part the result of the severity of his mental illness and chronic enduring thought disorder. As such, steps have been taken to anonymize the information contained in this report and remove all identifying information.
The authors declare no conflicts of interest.
Please send correspondence to: Xavier Boland, BMBS, MRCP, MRCPsych, Postgraduate Department, St Bernard’s Hospital, Uxbridge Rd., Southall UB1 3EU, UK (e-mail: email@example.com).
Compared with the general population, individuals with schizophrenia demonstrate an increased prevalence of obesity. While most antipsychotics are associated with weight gain, certain second-generation antipsychotics (SGAs) appear to be especially problematic.
Weight gain and obesity are highly distressing to these patients, can reduce treatment adherence, and may increase the relative risk of serious medical conditions and all-cause premature mortality. The selection of an antipsychotic on the basis of its effectiveness and relative side effect profile is recognized as an important initial consideration in the treatment of schizophrenia.
However, less is known regarding the efficacy of dietary, pharmacologic, and behavioral therapy in reducing antipsychotic-related weight gain and obesity. Behavioral therapy, in particular, is understudied, and there are relatively few controlled trials of its effectiveness in reducing SGA-induced weight gain.
Although weight loss resulting from behavioral therapy has been observed mostly as a result of effective short-term interventions, controlled behavioral studies do exist to suggest that weight can be controlled long term.
In addition, a small pilot study in patients with schizophrenia or schizoaffective disorder recently demonstrated that behavioral therapy that utilizes stepped interventions, involving body weight self-monitoring, diet, and exercise, can prevent weight gain in patients initiating treatment with SGAs.
Early Warning Signs | Schizophrenia Society of Saskatchewan
One of the difficulties of reading the early warning signs of schizophrenia is the easy confusion with some typical adolescent behavior. Schizophrenia can begin to affect an individual during the teen years, a time when many rapid physical, social, emotional, and behavioral changes normally occur. There is no easy method to tell the difference. It’s a matter of degree.
If you have any concerns, the best course of action is to seek the advice of a trained mental health specialist. The following list of early warning signals of mental illness was developed by families affected by schizophrenia:
Most Common Signs
- Social withdrawal, isolation, and suspiciousness of others
- Deterioration and abandonment of personal hygiene
- Flat expressionless gaze
- Inability to express joy
- Inability to cry, or excessive crying
- Inappropriate laughter
- Excessive fatigue and sleepiness, or an inability to sleep at night
- Sudden shift in basic personality
- Depression (intense and incessant)
- Deterioration of social relationships
- Inability to concentrate or cope with minor problems
- Indifference, even in highly important situations
- Dropping out of activities (and life in general)
- Decline in academic or athletic performance
- Unexpected hostility
- Hyperactivity or inactivity, or alternating between the two
- Extreme religiousness or preoccupation with the occult
- Drug or alcohol abuse
- Forgetfulness and loss of valuable possessions
- Involvement in auto accidents
- Unusual sensitivity to stimuli (noise, light, colour)
- Altered sense of smell and taste
- Extreme devastation from peer or family disapproval
- Noticeable and rapid weight loss
- Attempts at escape through geographic change; frequent moves or
- Excessive writing (or childlike printing) without apparent meaning
- Early signs of migraine
- Irrational statements
- Strange posturing
- Refusal to touch persons or objects; insulation of hands with paper,
- Shaving head or removal of body hair
- Cutting oneself; threats of self mutilation
- Staring, not blinking, or blinking incessantly
- Rigid stubbornness
- Peculiar use of words or language structure
- Sensitivity and irritability when touched by others
- Change of behavior: dramatic or insidious.
None of these signs by themselves indicate the presence of mental illness. Families who helped compile this list have indicated that they unfortunately had not acted on these early warning signs. With the benefit of hindsight and today’s knowledge about early intervention, family members are urged to seriously consider seeking medical advice if several of the behaviors listed above are present, or constitute a marked change from previous behavior, and persist over a few weeks.