Posted by iansf on May 31, 2004, at 11:31:00
F.Y.I.
REBOXETINE ATTENUATES OLANZAPINE-INDUCED WEIGHT GAIN
Olanzapine increases appetite and weight; the result is a poorer
body image and self-esteem, and a greater risk of medical
morbidity and mortality. Previously antipsychotic-naive patients
are more likely to gain weight with antipsychotic drugs, and the
weight gain is greater earlier rather than later during therapy.
Can olanzapine-induced weight gain in such contexts be prevented?
Poyurovsky et al (2003) addressed the issue in an Israeli
double-blind, randomized controlled study.The sample comprised 26 inpatients with first-episode DSM-IV
schizophrenic disorder, all of whom were prescribed olanzapine 10
mg/day. The mean age of the sample was about 31 years. The sample
was 65% male. The mean duration of illness was about 3 years. No
patient had previously received antipsychotic drugs for more than
one month.These patients were randomized to receive either reboxetine 2 mg
twice daily (n=13) or placebo (n=13) for 6 weeks. Anticholinergic
drugs and benzodiazepines were permitted if required; no other
psychotropic medications were allowed. No special diet or
exercise program was prescribed.Three patients dropped out of each group during the first week,
all because of agitation. No patient dropped out subsequently.
IMPORTANT FINDINGS WERE:
1. Mean weight gain was significantly lower in the reboxetine
group than in the placebo group (2.5 kg vs 5.5 kg, respectively).2. Significantly fewer reboxetine than placebo patients gained at
least 7% in weight, the cutoff for clinically significant weight
gain (20% vs 70% of study completers, respectively).3. In neither group was weight gain related to the baseline body
weight.4. Positive symptoms, negative symptoms, and global measures
improved comparably in both groups; the reduction in depressive
symptoms, however, was slightly but significantly greater with
reboxetine than with placebo.5. Adverse events did not differ significantly between the two
groups.
CONCLUSION
In olanzapine [10 mg/day]-treated patients with first-episode
schizophreniform disorder, reboxetine (4 mg/day) significantly
attenuates early weight gain and reduces depressive symptoms
without occasioning adverse effects of note.
COMMENTS
1. We do not know whether weight gain will increase after
reboxetine is withdrawn, or whether reboxetine will continue to
effectively attenuate olanzapine-induced weight gain in the long-
term. These issues require to be addressed in future research.2. We do not know whether reboxetine acts by decreasing
olanzapine-induced increase in appetite or by decreasing
olanzapine-induced somnolence and physical inactivity. We also do
not know whether reboxetine has a favorable effect on metabolic
markers such as the blood glucose and serum lipid profile. These
issues, too, require to be addressed in future research.3. Poyurovsky et al (2003) discussed adrenergic, serotonergic,
and histaminic mechanisms of weight gain. Reboxetine, a
norepinephrine reuptake inhibitor, obviously acts through
adrenergic mechanisms. It is possible that other antidepressant
drugs which do not block adrenergic, serotonergic, and histaminic
receptors may likewise attenuate olanzapine-induced weight gain;
examples of such drugs include the selective serotonin reuptake
inhibitors and venlafaxine. In this context, however, Poyurovsky
et al (2002) found that the addition of fluoxetine (20 mg/day for
8 weeks) did not attenuate olanzapine-induced weight gain in
young adults with first-episode schizophrenia and a short
duration of illness (20).
REFERENCES
Poyurovsky M, Pashinian A, Gil-Ad I, Maayan R, Schneidman M,
Fuchs C et al. Olanzapine-induced weight gain in patients with
first-episode schizophrenia: a double-blind, placebo-controlled
study of fluoxetine addition. Am J Psychiatry 2002; 159: 1058-
1060.Poyurovsky M, Isaacs I, Fuchs C, Schneidman M, Faragian S,
Weizman R et al. Attenuation of olanzapine-induced weight gain
with reboxetine in patients with schizophrenia: a double-blind,
placebo-controlled study. Am J Psychiatry 2003; 160: 297-302.
poster:iansf
thread:352361
URL: http://www.dr-bob.org/babble/20040527/msgs/352361.html