PsychRights®
Law Project for
Psychiatric Rights
Fava G: Do
antidepressants and antianxiety drugs increase chronicity in affective
disorders? Psychotherapy and
Psychosomatics 1994; 61: 125-131.
Presents important questions for researchers and clinicians,
raising possibility that antidepressants and benzodiazepines / barbiturates may
induce biological changes which lead to permanent symptoms, albeit less severe
than original in some cases. Fava is
defender of “drugs + therapy,” and criticizes the benzodiazepine critics whom
he calls “the narrow-minded damnation chorus.”
Nonetheless, he acknowledges the results of research showing that
chronic administration of xanax (alprazolam) is inferior to exposure therapy,
even when alprazolam is COMBINED with exposure therapy. In a study conducted in Toronto,
patients given the benzodiazepine for panic disorder with agoraphobia had long
term outcomes that were worse then psychotherapy alone. Similarly, Fava mentions the findings of the
Pittsburgh Study of Maintenance Therapies in recurrent depression, which
suggest that patients maintained on low doses of antidepressants become unable
to withdraw from drug treatment after three years. Fava raises questions about whether drugs
therefore may be causing more harm than good, by inducing chemical changes
which increase the sensitivity of individuals to the behavioral features of
anxiety or depression. Benzodiazepines
may be sensitizing the brain to anxiety by inducing downregulation of the GABA
A receptor, the putative mechanism responsible for panic attacks. Fava implies that there may be similar
adaptations occurring in the brain, which lead to permanent residual symptoms
of depression.
El-Mallakh RS, Waltrip C, Peters C: Can Long Term
Antidepressant Use Be Depressogenic?
Journal of Clinical Psychiatry
1999; 60 (4): 263.
Three clinicians in Louisville,
KY have written a letter to the Editor at
the Journal of Clinical Psychiatry, responding to an article (Rothschild and
Byrne) about loss of antidepressant
efficacy despite maintenance therapy with antidepressants. In the letter, the authors acknowledge the long-noted tendency of
antidepressants to induce mania and/or rapid cycling. They emphasize the tendency of long term
effects of drug treatments to vary widely from acute effects. A possible mechanism that may be responsible
for the medication-related induction of chronic depressive symptoms lies in anatomic changes: changes in neuronal number, or
changes in synaptic number. The authors cite several studies demonstrating these changes
in animals treated with antidepressants.
Either kind of change might render human subjects more susceptible to
depressive symptoms over time. In other
words, it is possible that antidepressants
-- just like neuroleptics – induce structural changes in the brain which
make symptoms refractory to treatment.
Byrne SE, Rothschild AJ:
Loss of Antidepressant Efficacy During Maintenance Therapy: Possible Mechanisms
and Treatments. Journal of Clinical
Psychiatry 1998; 59 (6): 279-288.
Authors look at frequency with which antidepressant
medication responders begin to experience return of depressive symptoms,
despite the continuation (maintenance) phase of drug treatment. The authors have performed a search of
Medline, reviewing 13 double-blind, placebo controlled studies
involving treatment with antidepressants for at least six months, between 1966
and 1997. They report a frequency of
relapsing/recurring symptoms while taking medication of 9 – 57%.
They also acknowledge that the
Hamilton Rating Scale for depression, used in most studies, probably
underestimates the frequency of
“relapse” during treatment due to the fact that it emphasizes vegetative
features. The authors acknowledge that
many more patients (more than 60%) who are continuing their treatment with
antidepressant medication experience the return of, or worsening, of depressed
mood, apathy, and fatigue. They suggest
a number of possible reasons for these effects, ultimately concluding that it
may be necessary to “raise doses” or
“add more medications” to compensate for the decreasing efficacy of
antidepressants.
Fava
GA:
Can Long Term Treatment With Antidepressant Drugs Worsen the Course of
Depression ? Journal of Clinical Psychiatry 2003; 64 (2): 123-133.
Author looks at possibility that antidepressants may worse
the course of depression in the long term.
He reviews the existing literature (Medline search) to find articles
describing the phenomena of tolerance, sensitization, or switching associated
with antidepressant therapy. He
concludes that continued drug treatment may “recruit” processes in the brain
that oppose the initial acute effects of drug treatment, and which increase vulnerability
to relapse during or after the continuation of medication. The author suggests that “antidepressants are
crucial in the treatment of major depressive episodes,” but he suggests that
they possibly worsen the overall course of the disorder they are intended to
relieve. Concerned about the paradoxical
effects of pharmacotherapy (long term treatment makes some patients worse), he
suggests that “further study is needed.”
Brugha TS, Bebbington PE, MacCarthy B, Sturt E, Wykes T:
Antidepressants may not assist recovery in practice: a naturalistic prospective
survey. Acta Psychiatrica
Scandinavica 1992; 86: 5-11.
In a study of 130 patients referred to Maudsley hospital for
further evaluation of depression, 119 were reassessed after a 4 month period of
treatment. All patients in the study
were interviewed within six months of the onset of their first depressive
episode, or within six months of a recurrent depressive episode. Of the 119 patients who were successfully
followed up at four months, 13 were admitted to an inpatient unit of the
hospital; 3 were admitted to a day hospital program; and all others were
continued either in outpatient psychiatric care (54), the care of their GP (29), or no
care (19 decided to pursue no further treatment). Results at follow-up showed a consistent
trend (although not robust) for a “worse outcome in those on drug
treatment.” Patients receiving drug
treatment in the study were no more ill (no worse) in the study than those who
did not receive it. 44 patients in the
study were not on medication at the time of the first interview. 16 of them were placed on medication – 30% of
these individuals recovered, compared to 50% (28 patients) who remained medication
free. Overall rates of recovery were
found to be 71% of untreated (not medicated)
vs. 61% of those on medication.
Fava
GA:
Potential Sensitising Effects of Antidepressant Drugs on Depression. CNS Drugs 1999; 12 (4): 247-256.
Fava presents evidence to support the hypothesis that
antidepressant drugs may sensitise the brain and worsen the long term
outcome. He suggests clinical findings
demonstrating unfavorable long term outcomes when patients are treated
pharmacologically. Fava includes the examples of antidepressant-induced depression,
anxiety, mania, and/or rapid cycling in some patients; the occurrence of
tolerance to the effects of drugs during long term treatment; the existence of
withdrawal syndromes following the discontinuation of antidepressant drugs; and
the onset of resistance when some patients are later rechallenged with the same
antidepressant drug. Fava supports the
use of antidepressants as a treatment for depression, but he believes that the
use of these drugs might need to be modified (limited) in order to prevent the
deleterious consequences of sensitization. He
recommends a cost-benefit appraisal of antidepressants, in order to avoid using
them for “prophylaxis,” for minor symptoms, or for anxiety. Fava
worries that the current trend of long-term antidepressant
administration may be counter-productive, due to the induction of brain changes
which contribute to diminishing drug response over time.
Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R: Sleep Changes After 4 Consecutive Days of
Venlafaxine Administration in Normal
Volunteers. Journal of Clinical
Psychiatry 1997; 58 (8): 348-350.
The authors present the results of a study involving 8
normal volunteers who were given venlafaxine (a combined noreinephrine /
serotonin reuptake inhibitor) for four consecutive nights. They studied the quality of sleep in these
subjects for two nights prior to the initiation of drug treatment, followed by
four nights consecutive nights during drug therapy. The volunteers were assessed in a sleep
laboratory, where the following measures were obtained: EEG, electrooculogram,
electromyogram, EKG, and thermistor measurements (nose and mouth). Findings were significant for reductions in
sleep stages I and III. REM sleep was
reduced after the first dose of venlafaxine, and was completely suppressed by
the fourth night. Six of the eight
volunteers experienced periodic limb movements of sleep (PLMS). Authors speculate that sleep disturbances
noted in this study may have been caused by abrupt rise in aminergic
neurotransmitters (norepinephrine, serotonin, dopamine), which are thought to
suppress REM sleep.
Clemes SR, Dement WC: Effect of REM Sleep Deprivation On
Psychological Functioning. Journal of
Nervous and Mental Disease 1967; 144
(6): 485-491.
Investigators examined six college students (age 18-20)
during a period of six nights of REM sleep deprivation, followed one week later
by six nights of non-REM sleep deprivation (or vice versa). Subjects were tested with certain
neuropsychological instruments on days seven and fourteen, in order to see if
changes in sleep patterns were associated with any significant changes in
cognition or behaviors. Results
suggested that REM deprivation may cause reductions in ego control, as
reflected in this study by changes in critical thinking skills (less concern about
matching concepts to physical outlines in the Holtzman inkblot). These changes were not found to be caused by
fatigue or sleepiness.
Subjects were also evaluated for changes in ‘reality testing’ after REM sleep deprivation, with marked
changes noted in one subject. Responses
to the TAT (thematic apperception test) suggested an increase in “intensity of
need” and “intensity of feeling” (emotionality) following REM sleep
deprivation. The authors of the study
suggest that REM sleep deprivation stimulates in humans – as in animals – an
increase in certain instinctive drives.
Vasar V, Appelberg B, Rimon R, Selvaratnam: The effect of fluoxetine on sleep: a
longitudinal, double-blind polysomnographic study of healthy volunteers. International Clinical
Psychopharmacology 1994; 9: 203-206.
Investigators administered fluoxetine (prozac) and placebo
in a randomized, double blind trial involving 12 healthy volunteers. Subjects had polygraphic (sleep) recordings
performed at home twice before and once after receiving medication for six
days. Fluoxetine was associated with a
significant reduction in total minutes of REM sleep, percentage of sleep spent in REM, and an increase in REM
latency. Actual sleep time was not
affected. The Symptom Check List-90
(SCL-90) was also completed before and after treatment with fluoxetine. The 90 items on the check list include
symptom dimensions including: somatization, obsessive-compulsive items, interpersonal
sensitivity, depression, anxiety, anger-hostility, paranoia, and
psychoticism. A significant change
(decrease) was found only in the subscale on “interpersonal sensitivity,” which
could be interpreted either as a reduction in “rejection sensitivity” or,
alternatively, as an increase in feelings of indifference towards the thoughts
or opinions of others. The authors
conclude that their polygraphic findings are consistent with the findings of
other investigators, noting that most antidepressants suppress REM sleep.
Winkelman JW, James L: Serotonergic antidepressants are
associated with REM sleep without atonia.
Sleep 2004; 27 (2): 317-321.
Authors report the results of a study involving a sleep lab
investigation of 15 subjects receiving a serotonergic antidepressant (prozac,
paxil, celexa, Zoloft, effexor) vs. 15 age –matched controls not taking any
such medication. Subjects were recruited
from a polysmonography database at Sleep Health Centers in Newton
Center, MA. The investigators performed a chart review,
analyzing clinical and sleep data for subjects referred to their center for the
evaluation of a sleep disorder. None of
the subjects included in the study were diagnosed with sleep apnea, which was
the primary reason for referral. The
investigators performed a retrospective analysis of the sleep studies,
concentrating on EMG tone (muscle tone) changes during REM sleep in individuals receiving chronic treatment with serotonergic
antidepressants. Interestingly, these
were subjects who did not have any complaints of abnormal behavior during
sleep. Findings were significant for
increased submental activity during REM among subjects taking antidepressants,
with 13% of the subjects in this study exceeding Gagnon’s criteria for REM
sleep behavior disorder (RBD); 53% exceeding Eisensehr’s criteria for RBD. The authors of this study conclude that the
clinical status of REM sleep without atonia – as seen in their patient sample –
remains ambiguous. Even so, they express their concerns that REM sleep without
atonia may be an early stage of RBD.
They suggest that there are substantial potential public health
implications of REM sleep abnormalities in individuals taking serotonergic
antidepressants, particularly in the context of more than 10 million people in
the US alone taking these drugs.
[Note: the significance of RBD is as follows: during
normal REM sleep, the muscle tone of the body is inhibited or “turned off” so that the sleeper does not act
out, physically, the scenes of a dream.
RBD is a form of “wakeful dreaming” during which a person is technically
asleep, but moving – it can lead to the enactment of violent or otherwise
injurious behaviors, as the person literally acts out his or her dreams.]
Wallace WAH, Balsitis M, Harrison BJ: Male breast
neoplasia in association with selective serotonin reuptake inhibitor therapy: a
report of three cases. European Journal
of Surgical Oncology 2001; 27: 429-431.
The authors are surgeons in the UK,
who describe three cases of carcinoma of the breast in male patients, all of
whom had exposure to SSRIs (serotonin reuptake inhibitors). Carcinoma of the male breast is an
extremely rare form of breast cancer, occurring in less than 1% of all
cases. This paper describes three male
patients who presented with neoplastic or pre-neoplastic breast disease, all of
whom were prescribed SSRIs prior to their surgical consultations. The authors of this article suggest that
SSRI-related breast cancer may be more easily assessed in male populations, due
to the absence of complex physiological changes in the male breast throughout
life. The authors also discuss several
epidemiological studies revealing increased risks of breast cancer in women
using SSRIs (2-7 fold higher risk, relative to women not using SSRIs).
Cotterchio M, Kreiger N, Darlington
G, Steingart A: Antidepressant Medication Use and Breast Cancer Risk. American Journal of Epidemiology 2000; 151 (10: 951-957.
Authors note that 30% of all newly diagnosed cancers in
females are breast cancers, and that 19% of all female cancer-related deaths
are due to breast cancer. At the same
time, they note an increase of breast cancer incidence of 20-25% between the
early 1970s and the early 1990s.
Recognizing the increasing use of antidepressant medications in women,
and noting the connection between antidepressants and breast cancer risk in
animals, the authors performed a case-control study using the
Ontario
(Canada) Cancer
Registry. They identified breast cancer cases in women age 25-74 yrs,
diagnosed between 1995 and 1996.
Population controls were identified using property assessment
rolls. Subjects were asked about
antidepressant use, with subjects excluded if they had reported less than 2
weeks’ duration of treatment; or if they had taken antidepressant medication
only in the six month period immediately prior to their breast cancer
diagnosis. The use of tricyclic
antidepressants for greater than two years was associated with a two-fold
elevation in breast cancer risk. The use
of paroxetine (paxil) was associated with a seven-fold elevation in breast
cancer risk. There was no association
between duration of SSRI use and breast cancer risk. Possible mechanisms for the risks in this
study include: stimulation (by paroxetine) of prolactin secretion, which has
been implicated in the etiology of breast cancer; inhibition of the P450 2D6
enzyme (which may lead to a reduced clearance of carcinogens and estrogen by
the liver); and/or stimulation of benign proliferative breast disease, which
may be precursor to breast cancer. The
authors conclude that there remains a paucity of epidemiologic studies in this
area, and they express concerns about the long-term use of antidepressants.
Preda A, MacLean RW, Mazure CM, Bowers MB, Jr: Antidepressant-Associated Mania and Psychosis
Resulting in Psychiatric Admissions.
Journal of Clinical Psychiatry
2001; 62 (1): 30-33.
The authors report their findings of a retrospective chart
review of all admissions to their university-based hospital psychiatric unit
over a 14 month period. They reviewed
the records of 533 consecutive admissions to the inpatient service at
Yale-New
Haven Hospital
between 1/97 and 2/98. Patients
included in the study were subjects experiencing the onset or exacerbation of
mania and/or psychosis as the primary reason for admission; antidepressant use
at the time of admission; recent initiation (within 16 weeks) of antidepressant
therapy; and rapid improvement following the discontinuation of antidepressant
therapy (along with the addition of a neuroleptic or mood stabilizer, if
indicated). Excluded from the study were
all individuals severe personality disorders; concurrent substance use
disorders; stable medication regimens at admission; or patients who had
recently undergone reductions in neuroleptic dose. Despite this conservative approach (with
numerous exclusions), the investigators discovered that 8% of the patients
admitted to the inpatient unit fit the profile of anti-depressant induced mania
or psychosis. The authors conclude that the rate of admissions due to
antidepressant-associated behavioral effects remains significant.
[Note: The findings
of this study were consistent with an earlier study by the same authors, in
which they found that 11% of the consecutive admissions to their inpatient unit
over a period of six months were associated with antidepressant therapy.
Given the fact that these Yale studies focused only upon
patients whose symptoms were severe enough to require hospitalization, it is
quite likely that the actual rates of antidepressant-induced mania and/or
psychosis are higher than these studies suggest.]
Leo RJ: Movement Disorders Associated With the Serotonin
Selective Reuptake Inhibitors. Journal
of Clinical Psychiatry 1996; 57 (10):
449-454.
The author reviews the medical literature (Medline and
bibliographies) for case reports of SSRI-induced movement disorders. Acknowledging the limitations of adverse
event reporting systems (namely, that all such cases are spontaneously
reported), Leo concedes that the prevalence of SSRI-associated motoric effects
cannot be generated from the published literature. Nonetheless, he inventories the 71 case
reports of de novo motor symptoms arising in patients after the initiation of
SSRIs. Among the movement disorders
noted are: akathisia (45% of cases); dystonia (28%); parkinsonism (14%); tardive dyskinesia-like movements (11%); tremors (10%). Pathophysiologic mechanisms thought to be
responsible for these effects include: inhibitory effects of serotonin fibers
upon extrapyramidal neurons; SSRI inhibition of dopamine synthesis (and other
catecholamines) in the forebrain, striatum, and/or hippocampus; interaction
between serotonergic neurons and GABA or cholinergic pathways; or
SSRI-induction of hypersensitivity in postsynaptic dopamine receptors. The author concludes that further controlled
studies comparing movement disorders among SSRI- and placebo treated patients
are required.
Ditto, KE: SSRI Discontinuation syndrome: Awareness as an
approach to prevention. Postgraduate Medicine
2003; 114 (2): 79-84.
The author highlights the symptoms which characterize the
SSRI discontinuation syndrome, noting a frequency of occurrence as high as 25%
in patients who stop taking those agents abruptly. Ditto offers Malcolm Lader’s definition of a
withdrawal syndrome:
“well-defined syndrome with predictable onset, duration, and
offset of action containing psychological and bodily symptoms not previously
complained of by patients.”
The article
calls attention to the fact that SSRI discontinuation symptoms can begin within
1-3 days of abruptly stopping (or tapering) SSRI therapy, and can continue for
several weeks if not treated. Features
include anxiety, crying spells, insomnia, irritability, nausea, vomiting,
dizziness, headache, paresthesias, dystonia or tremor, chills, fatigue, muscle
pain, or runny nose. The author
suggests that SSRI discontinuation syndrome occurs most commonly in individuals
who have taken such drugs for less than 6-8 weeks. The article discusses differential diagnoses, noting that
SSRI discontinuation syndrome is easily overlooked (not considered or
recognized), easily prevented (patient education, slow tapers,
avoidance of missed or expired doses), and easily managed (resumption of
previous drug, substitution of longer-acting drug, or initiation of slow
taper).
Liu BA, Mittmann N, Knowles SR,
Shear NH: Hyponatremia and the
Syndrome of Inappropriate Secretion of Antidiuretic Hormone Associated with the
Use of Selective Serotonin Reuptake Inhibitors: A Review of Spontaneous
Reports. Canadian Medical Assocation
Journal 1996; 155 (5): 519-527.
The authors conducted a review of SSRI-associated SIADH as reported in the
medical literature (30 published cases) and unpublished case reports held by a
variety of authorities (e.g., pharmaceutical industry, FDA, Health Protection
Branch of Ontario, the World Health Organization). SIADH (syndrome of inappropriate antidiuretic
hormone) is a potentially life-threatening disorder which can result in
dangerously low levels of sodium, seizures, coma, and death. The authors of this study reviewed published
reports
Between 1980 and 1995.
83% of the published cases, and 74% of the unpublished cases, involved
patients age 65 or older. 75% of the
cases occurred within 30 days of initating therapy. The exact mechanism of SSRI-associated SIADH
remains unknown, but possible causes include:
effects on dopamine, as neuroleptics have been known to facilitate ADH
secretion; effects on norepinephrine (stimulation of ADH via alpha-2
receptors); 5HT2 or 5HT1C receptor mediation of ADH release; peripheral effects
on the renal medulla; or the re-setting of the body’s osmostat, resulting in a
lower threshold for the secretion of ADH.
The authors conclude that SIADH may be a significant health risk related
to the use of SSRIs in older patients.
However, they acknowledge the fact that further research is needed in
order to determine the incidence of this adverse effect, and in order to
establish the relative risk of SSRI-induced hyponatremia among different (all)
age groups.
Weintrob N, Cohen D, Klipper-Aurbach Y, Zadik Z, Dickerman Z: Decreased Growth During Therapy With
Selective Serotonin Reuptake Inhibitors. Archives of Pediatric and Adolescent
Medicine 2002; 156: 696-701.
Authors report on 4 patients (age 12 to 14) treated with
SSRIs who all experienced significant growth suppression when their pubertal
growth spurt was expected. Three of the
patients demonstrated a decreased growth hormone response to a clonidine
stimulation test; two of the patients showed diminished response to both
clonidine and glucagon stimulation tests; and one subject displayed a decreased
24-hour secretion of growth hormone which normalized immediately upon the
cessation of SSRI therapy. The authors
conclude that a decrease in growth rate may occur during SSRI therapy, and that
the expanding use of these drugs – particularly, in young age groups – warrants
larger studies to investigate their effects upon growth and growth hormone
secretion.
Birmes P, Coppin D, Schmitt L, Lauque D: Serotonin
syndrome: a brief review. CMAJ 2003; 168 (11): 1439-1442.
The authors describe two short case reports involving
serotonin syndrome. The article is a
review of serotonin syndrome, outlining the major and minor symptoms, their
cause, and their management. Serotonin
syndrome is a potentially fatal reaction to any of a variety of medications
that increase serotonergic tone in the central nervous system. Symptoms include behavioral changes (insomnia, agitation),
neurological effects (confusion, obtundation, hyperreflexia, myoclonus,
tremors, seizures, coma), and autonomic dysregulation (hyperhidrosis, rapid
heart rate, elevated BP, fever). Other
symptoms include GI distress (nausea, vomiting, diarrhea); changes in white
blood cells; and elevated creatine kinase.
The authors propose a variety of possible cellular mechanisms leading to
these symptoms: overstimulation of serotonin (5HT1A) receptors in central gray
nuclei and medulla; overstimulation of 5HT2 receptors; inhibition of SSRI metabolism by other drugs;
excessive synthesis or release of serotonin.
Treatment involves immediate discontinuation of SSRIs, IV fluids to
prevent risk of myoglobinuria (and kidney failure), and other stabilizing
measures as needed (cooling bed, mechanical ventilation, anticonvulsants,
anxiolytics, antihypertensive agents).
Some studies have suggested benefits with the use of beta-blockers,
which may reduce symptoms through their concomitant antagonism of 5HT1A receptors. Other possible treatments include serotonin
antagonists (such as cyproheptadine) and/or neuroleptics (such as
chlorpromazine, ziprasidone) which block 5HT1A receptors. Authors emphasize importance of patient
education, limitation of polypharmacy, and use of “drug holidays.”
Carbone JR: The Neuroleptic Malignant and Serotonin
Syndromes. Emergency Medicine Clinics of
North America 2000; 18 (2): 317-325.
Author discusses NMS (neuroleptic malignant syndrome) as a
rare, idiosyncratic reaction to antipsychotic therapies. Incidence of NMS is estimated to be 1%. Article discusses the features of NMS, its
pathophysiology, diagnosis, and management.
The author then moves on to discuss the “serotonin syndrome”: a toxic
effect of SSRIs (and/or other drugs) believed to arise from the
over-stimulation of 5HT1A receptors in the brain and spinal cord. Features include mental status changes,
neuromuscular and autonomic dysregulation.
Patients with NMS are more apt to experience high fevers, swallowing
difficulty, incontinence, drooling.
Patients with SS (serotonin syndrome) are more likely to present with GI
(gastrointestinal) side effects, such as diarrhea or vomiting. In addition, SS patients are more likely to
demonstrate shocklike contractions in muscles (myoclonus), hyperreflexia, and
ataxia. Treatment involves immediate
removal of the offending agent(s). Use
of dopamine antagonists is recommended with reservation by this author, due to
the fact that NMS would be made worse by neuroleptic therapy (and NMS can
easily be confused for SS). The use of
serotonin antagonists has been recommended by some. Propranolol (beta-blocker, recommended for
its theoretical role in blocking 5HT receptors) has been associated with at
least one death in a patient with SS. The
mainstays of treatment for SS include removal of the offending agent, supportive care (IV fluids), judicious use of
benzodiazepines, and intensive monitoring (e.g., ICU admission).
Martin TG: Serotonin Syndrome. Annals of Emergency Medicine 1996; 28 (5): 520-526.
SSRIs have largely replaced tricyclic antidpressants (TCAs)
in the USA. The author proposes that the consequences of
SSRI-poisonings (overdose) have tended to be less serious than TCA overdoses. However, Martin suggests that the incidence
of adverse effects and drug interactions is greater. He describes the characteristic features of
serotonin syndrome (mental status changes, autonomic dysfunction, neuromuscular
abnormalities); its most common precipitants, differential diagnoses, and
treatment. Author makes important points: bromocriptine and dantrolene
(two treatments commonly recommended for NMS) may actually worsen SS by
increasing 5HT levels in the brain. Similarly, the use of serotonin antagonists (methysergide,
cyproheptadine) and beta-blockers (propranolol) are recommended only with
caution. At least one patient developed
SS and died from it, despite treatment with propranolol at the time that the
serotonin syndrome emerged. The author
therefore recommends careful supportive care: use of cooling measures,
sedatives, anticonvulsants, antihypertensives, mechanical ventilation and
paralytics (to reduce excessive muscle activity and hyperthermia), if required. While serontonin syndrome can be mild to
moderate in severity and self-limited (resolving in 24-72 hours), some cases can be
severe, lethal, and longer lasting (with some residual symptoms persisting for
weeks).
Note:
A quick word about REM sleep, and why drug-induced REM
suppression is concerning. Researchers
discovered that many depressed patients appeared to have an increase in REM
sleep compared to non-depressed individuals.
They also noted the impact of antidepressant drugs upon REM sleep. As a result, psychiatrists began to
experiment with REM sleep deprivation as a potential treatment for depression
back in the 1970s and 1980s. This
practice fell out of favor, due to poor reproducibility of results, mixed findings,
and short-acting benefits. More
recently, studies investigating REM sleep and its association with depression
have suggested that REM sleep decreases as individuals recover from depression. Since most of the antidepressants suppress
REM sleep chronically, the continuation
of such treatments past the point of symptom remission may actually go too
far, ultimately contributing to mood and
cognitive disruption.
REM sleep is more than the “phase of sleep” in which 90% of
human dreaming occurs. REM sleep is thought to be essential for learning and
memory. The suppression of REM sleep may therefore impair the acquisition and retrieval of
new information, the formation of long term memory, the maintenance of
procedural skills, and the overall capacity for cognitive flexibility.
