When the SSRI antidepressant medications came out about 10 years ago
they were thought to be a panacea for the mentally ill. Side effects
were few, no weight gain was expected as had been one of the biggest causes
of non-compliance in prior antidepressants.
But the proof would be in the pudding as long term effects including
weight gain, insomnia and sexual dysfunction began to emerge.
Some argue that the weight gain is due to the alleviation of depression,
the patient feeling better and eating more.
Many, particularyly patients who have experienced the weight gain disagree.
See my article Links
between Atypical antidepressants and Weight Gain denied
The following article is
Clinical Psychiatry News
and has been reprinted here for your information.
Long-Term Side Effects Surface With SSRIs
Author: Carl Sherman, Contributing Writer
[Clinical Psychiatry News 26(5):1, 1998. © 1998 International Medical
Insomnia, weight gain, sexual dysfunction emerge as problems
NEW YORK -- Physicians are seeing long-term side effects with selective
serotonin reuptake inhibitors far in excess of what was expected from
data, Dr. Norman Sussman said at a psychopharmacology update sponsored
New York University.
If these particular side effects -- sleep disturbances, sexual dysfunction,
gain -- are problematic for patients, one of the newer non-SSRI antidepressants
may be a better choice, he said. Of course, these drugs have their
side effect profiles.
When SSRIs first appeared a decade ago, their favorable side effect
profile was a
key selling point. They were clearly safer and easier to use than tricyclics
monoamine oxidase inhibitors and, above all, better tolerated by patients.
But experience has shown that some side effects are more common and
than initially expected, said Dr. Sussman, director of the psychopharmacology
research and consultation service at Bellevue Hospital Center in New
Depression is a chronic, recurrent disorder, so long-term side effects
be more important than acute ones in terms of patient compliance and
quality of life,
and this has come to guide Dr. Sussman's choice of antidepressants.
Early-onset side effects may be responsible for rapid withdrawals from
but some of the most troubling of these -- nausea, diarrhea, headache,
-- will remit in 2-3 weeks.
A knottier problem is adverse effects that persist as long as the patient
medication, such as sexual dysfunction and sleep disturbances. Also
troubling are those, like weight gain, that don't even develop until
late in treatment.
"These are the ones that are not in the insert, which is based on short-term
Dr. Sussman said.
Significant insomnia affects 15%-20% of patients taking SSRIs, twice
the rate with
placebo. Polysomnography has consistently found that these drugs cause
during the night: In addition to insomnia, bruxism, sweating, and periodic
movement are common. Vivid dreams and nightmares also occur. With ongoing
treatment, increasing numbers of patients report lethargy and fatigue,
"There are a lot of data showing that people who sleep poorly are more
relapse and that suicide risk is higher," he said.
Sleep problems often require concurrent medication: 22%-34% of patients
SSRIs also are prescribed sedatives or hypnotics, Dr. Sussman said.
Sexual dysfunctions are among the most distressing SSRI side effects.
libido and delayed or absent orgasm are the best known, but there are
as the "yawning-excitement syndrome." Patients experience sexual arousal
they yawn, often progressing to orgasm. "This is probably underreported.
often say, 'If you hadn't asked me, I wouldn't have mentioned it,'"
Perhaps the most unexpected SSRI-related problem to emerge has been
gain, which often begins only after several months of therapy. This
side effect has not
been shown to be frequent or severe in controlled studies but has been
occur in 18%-50% of patients in some open-label studies.
Because this runs counter to the image of the drug, many physicians
and patients are
unprepared to deal with it. "Some physicians tell patients, 'I can't
you're gaining weight -- you're on an SSRI,'" Dr. Sussman said.
Greg Keuterman, a spokesman for Eli Lilly & Co., manufacturer of
(fluoxetine), declined to comment except to point out that "this is
"We're approved by the FDA for long-term treatment of depression," he
Pfizer Inc., the maker of Zoloft (sertraline), and SmithKline Beecham
Pharmaceuticals, the maker of Paxil (paroxetine), did not respond to
These observations do contrast with what the clinical trials submitted
to the Food
and Drug Administration by pharmaceutical companies show, Dr. Sussman
would be nice if these long-term side effects were studied in clinical
Some of the newer antidepressants are less likely to cause the types
problems that lead patients to discontinue SSRIs, he said.
Of course, it is possible that unexpected side effects will emerge over
the long term
with these antidepressants as well, Dr. Sussman said.
With venlafaxine (Effexor), "the side effects are the same as with SSRIs:
somnolence, lethargy and fatigue, and weight gain, but they are less
new extended-dose formulation causes lower peak plasma levels, which
make the drug more tolerable. Notably less significant is nausea, which
problem with the immediate-release form of venlafaxine, Dr. Sussman
Mirtazapine (Remeron) causes no gastrointestinal problems, sexual dysfunction,
insomnia over the long term, but difficulties are likely to occur early.
be advised that while somnolence at the start of therapy may be "overwhelming,"
usually lasts only 2-3 days. "You need to counsel patients to stick
with it," he said.
Increased appetite and weight gain also may be marked in the first stage
but will generally plateau after 2-3 months. "[Treatment with mirtazapine]
only if the patient trusts you that these effects are time limited
and treatable," he said.
European trials of mirtazapine reported less trouble with initial weight
somnolence, perhaps because higher doses were used. "Most [clinicians]
on starting at 30 mg rather than 15 mg," Dr. Sussman said.
Nefazodone (Serzone) appears to cause little sexual dysfunction and
agitation and carries a low risk of weight gain. It enhances sleep
quality and reduces
awakenings. The most common side effects -- nausea, sedation, and dizziness
generally limited to the beginning of treatment and are dose related.
with each week of treatment," he said.
Physicians should be aware of the fact that patients who are switched
SSRIs to nefazodone experience a higher than expected rate of side
Once-daily dosing in the evening can minimize daytime sedation and dizziness
nefazodone in patients who have been stabilized on the standard twice-a-day
schedule, he said.
Bupropion (Wellbutrin) has been associated with headache, nausea, and
but it is well tolerated by most patients, particularly in the long
sustained-release form appears to reduce seizure risk, which has been
with the drug. But bupropion still should not be given to patients
who may be prone
to seizures, Dr. Sussman said.