Antidepressant Withdrawal Syndrome: Findings, Recommendations, and Resources | Psychology Today

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Antidepressant Withdrawal Syndrome: Findings, Recommendations, and Resources

By Lane, Ph.D. on July 17, 2011 - 7:52am

In his " Defense of Antidepressants​ " in last Sunday's New York Times,

Kramer tried to discredit recent meta-analyses of SSRI antidepressants

that show most of their efficacy is owing to the placebo effect, to the point

where the difference between those antidepressants and placebo is " clinically

meaningless. " As Kramer repeatedly mischaracterized the very research he

summarized, I found his defense of the drugs wholly unpersuasive. Even so, it

was striking that his relatively long op-ed essay had nothing to say about

well-documented cases of withdrawal symptoms among those trying to end SSRI

treatment.

In May 2007, to invoke a quite different perspective on antidepressants in the

same newspaper, Bruce Stutz wrote a long and thoughtful piece​ on his own

difficulties ending a treatment of Effexor (Venlafaxine). Stutz also reported

some of the clinical literature to-date on the phenomenon.

In 1997, he explained, " nearly a decade after the introduction of Prozac, its

manufacturer, Eli Lilly, sponsored a research symposium to address the

increasing number of reports of patients who had difficult symptoms after going

off their antidepressants. By then it had become clear that drug-company

estimates that at most a few percent of those who took antidepressants would

have a hard time getting off were far too low. Jerrold Rosenbaum and Maurizio

Fava, researchers at Massachusetts General Hospital, found that among people

getting off antidepressants, anywhere from 20 percent to 80 percent (depending

on the drug) suffered what was being called antidepressant withdrawal (but

which, after the symposium, was renamed ‘discontinuation syndrome'). " (The

percentages noted in the study in fact ranged from 22% to 78% of patients

discontinuing​, with 78% still representing a distressingly high number.)

" The symptoms of discontinuation syndrome could be fierce, " Stutz added, as he

recounted in considerable detail, at varying doses, his own harassing problems

with " brain zaps, " panic attacks, insomnia, and despair on lower and lower doses

of Effexor. Fava, he noted, went on to publish in 2006 a paper citing further

withdrawal symptoms, such as " agitation, anxiety, akathesia, panic attacks,

irritability, aggressiveness, worsening of mood, dysphoria, crying spells or

mood lability, overactivity or hyperactivity, depersonalization, decreased

concentration, slowed thinking, confusion and memory/concentration

difficulties. " To the authors, these symptoms and their widespread recurrence

looked increasingly like a drug-related syndrome.

After Rosenbaum and Fava drew clinical attention to " discontinuation syndrome, "

several more studies unearthed comparable difficulties among those trying to end

SSRI antidepressant treatment. Sometimes couched as a dependency issue, and

sometimes also mistakenly viewed as a form of relapse in which the original

depression or anxiety treated is said to recur, withdrawal symptoms from

antidepressants have come to be seen among these researchers as a serious

pharmacological problem in their own right. The symptoms stem, the

researchers argue, from the neurological effects of the drugs' retention of

serotonin and the consequent downregulation of neurotransmitters that are once

again needed (though in short supply) when treatment ends.

As Kramer's silence on the topic last week helps illustrate, however, there has

been enormous resistance among advocates of SSRIs (and, naturally, among their

manufacturers) to addressing the topic and issue. Only recently have a few

researchers tried to isolate for withdrawal syndrome, rather than group such

symptoms with adverse effects and with assumptions about relapse.

In " Rebound Syndrome: When Drug Treatments Fail, " a chapter of my book Shyness:

How Normal Behavior Became a Sickness​, I focused extensively on

GlaxoKline's own " product monograph " for Paxil (Paroxetine hydrochloride),

which the drug-maker updated in 2005, following a chorus of complaints about the

drug's well-documented side effects. Those bear a rather startling resemblance

to the discontinuation syndrome that Rosenbaum and Fava earlier documented. The

side effects range, the drug-maker conceded, all the way from " agitation,

anxiety, headache, tremor, confusion, diarrhea, nausea, vomiting, and sweating "

to " mental status changes that include extreme agitation progressing to delirium

and coma " (qtd. p. 142; the manual can be downloaded here​).

" Recent analyses " of the drug's effect on patients under the age of 18

recognized " behavioral and emotional changes, including an increased risk of

suicide ideation, " GSK noted with obvious reluctance, following the FDA's

decision in August the previous year (2004) to add a black-box warning about

the drug-related risks of suicide on teens and young adults prescribed the

antidepressant.

Since the list of " severe agitation-type adverse events " in teens and adults

included " self-harm or harm to others, " GSK went on to add, as well as

" disinhibition, emotional lability, unpredictable mood swings, hostility,

aggression, depersonalization, [and] akathisia, " a serious condition marked by

extreme motor restlessness, apparently none of the several million people taking

the drug could safely be said not to require " rigorous clinical monitoring for

suicidal ideation " --an almost unbelievable outcome, voiced by the

drug-manufacturer itself, for a company still encouraging the public to take

Paxil for anxiety about going to parties and fear of being criticized. As USA

Today noted at the time​, " 20 percent of patients treated with Paxil in

worldwide clinical trials in major depressive disorder and 16.1 percent of

patients treated with Paxil in worldwide trials in social anxiety disorder . . .

discontinued treatment due to an adverse event. "

In the same chapter, I documented further evidence of such " adverse events " by

citing the extant literature on discontinuation syndrome and interviewing one

member of paxilprogress.org who has continued to track the research on SSRIs

and withdrawal syndrome with impressive diligence and care. " Kate, " as she's

dubbed in the book, following her request for anonymity, described to me at the

time how she was given Paxil because she thought she had social anxiety

disorder, and how, after initially responding well to the drug, she carefully

tapered her dose when she felt better. " I immediately had a whopping reaction, "

she despaired. " Three months of quasimania . . . followed by six months of

anxiety, insomnia, periodic brain zaps, and total uninterest in sex. " Other

drugs, prescribed by " well-meaning psychiatrists, " only worsened her anxiety,

weepiness, and sense of hopelessness. She said she felt worse, coping with

Paxil's aftereffects, than she did before starting treatment.

There are clear neurological reasons, Kate explained and follow-up research

corroborated, why an SSRI antidepressant like Paxil would generate a withdrawal

syndrome. First, while this class of drugs artificially raises the amount of

serotonin in the brain, the serotonergic system doesn't ignore the increase, but

adjusts to and compensates for it, downregulating the number of 5-HT1A

receptors because the drugs, altering serotonin levels, put them in less

demand. At the same time, the serotonergic system needs more 5-HT2 receptors to

soak up the excess of the messenger, a situation many studies have linked to

patients' widespread complaints of sexual dysfunction, because those receptors

send saturation signals to the brain. In 2002, in the International Journal of

Neuropsychopharmacology, to invoke just one study, Adam Opbroek and his

colleagues found that " 80% of patients with SSRI-induced sexual dysfunction also

describe clinically significant blunting of several emotions " (p. 147).

When patients try to end treatment, even stepping down their dose very

gradually, many of them (22% to 78%, according to Rosenbaum and Fava) find that

the receptors in their serotonergic system--saturated artificially for months,

even years--experience the drop to predrug levels as starvation. Some patients

then find themselves at the mercy of hair-trigger symptoms that register as

intense anxiety, aggression, and insomnia.

Several receptors--including 5-HT1A--aren't especially malleable, moreover, and

take longer to sprout anew after drug treatment ends, delaying the patient's

return to neuronal health. Indeed, some studies I consulted found that in

certain patients those receptors fail to grow back at all, in effect leaving the

patients worse off than before. (See for instance " Dissociation of the

Plasticity of 5-HT1A Sites and 5-HT Transporter Sites​ " in Paxil Research

Studies 19.3 [1994], 311-15.)

As the proportion of SSRI-takers found to suffer from discontinuation syndrome

is, by pharmacological standards, astronomical, and " one in ten

Americans " --roughly 30 million people in the U.S. alone-- " ingests " the drugs

each year, as Kramer noted only last week​, it seems incredible that

clinical trials have been so slow to recognize, and isolate for, withdrawal

syndrome in patients trying to taper and end SSRI treatment. The number of

people affected would, in any normal situation, drive a lot more targeted

research on the problem.

However, while drug-companies have done their best to redefine withdrawal

syndrome as relapse, to confuse doctors and patients into thinking the original

depression or anxiety had returned, the good news is that research is starting

to focus exclusively on the widespread problem of SSRI withdrawal syndrome.

Today, in her 7th year of recovery from severe Paxil withdrawal syndrome,

" Kate " --also known as " Altostrata " --runs a website called " Surviving

Antidepressants​ " that compiles research and data explicitly on the syndrome.

She is still " hypersensitive to neuroactive medications, " she reports, and

recovering from severe setbacks 33 months after discontinuation, but with the

help of a doctor who treats and has studied withdrawal syndrome, she is slowly

recovering.

In addition to providing peer support for patients struggling to end their

SSRI-treatment without massive, harmful problems, " Surviving Antidepressants "

notifies readers of research-in-progress, including work by Dr. Carlotta

Belaise, a colleague of Fava's and a frequent co-author with him of scientific

papers challenging the long-term use of antidepressants. While Dr. Fava's

research recently has been publicized on sites such as The Daily Beast​, Dr.

Belaise, a research fellow in the Affective Disorders Program of the department

of psychology at the University of Bologna, Italy, is collecting data on

antidepressant withdrawal syndrome​, " which, " she writes,  " we strongly

believe is a very important, common and delicate clinical problem. "

Precisely because of that delicacy, patients concerned about the drugs' adverse

effects should NOT terminate their treatment abruptly, but should instead taper

their dose very carefully and gradually, over a course of several months, always

in consultation with their doctor, to ensure their own safety.

What follows is a list of links to articles (compiled by Altostrata for this

blog), which those wanting to know more about SSRI withdrawal syndrome will find

on " Surviving Antidepressants. " The vast numbers of people suffering from this

syndrome are very much in Altostrata's debt for helping to document this

phenomenon and for giving it the medical attention it so clearly needs and

deserves. I will be reporting on Dr. Belaise's study on this blog when it is

published.

Further References

(2011) " Blue Again: Perturbational Effects of Antidepressants " :

http://survivingantidepressants.org/index.php?/topic/749-2011-blue-again-perturb\

ational-effects-of-antidepressants/​

Background

(2001) " Antidepressant Discontinuation Syndromes: Common, Under-recognized and

Not Always Benign " :

http://survivingantidepressants.org/index.php?/topic/781-2001-antidepressant-dis\

continuation-syndromes-common-under-recognised-and-not-always-benign/​ 

Frequency

(2003) " SSRI Discontinuation Syndrome " :

http://survivingantidepressants.org/index.php?/topic/824-2003-ssri-discontinuati\

on-syndrome/​

(2005) " Do Antidepressants Cause Dependence? " :

http://survivingantidepressants.org/index.php?/topic/826-2005-do-antidepressants\

-cause-dependence/​

(2006) " The Nature of the Discontinuation Syndrome Associated with

Antidepressant Drugs " :

http://survivingantidepressants.org/index.php?/topic/822-2006-the-nature-of-the-\

discontinuation-syndrome-associated-with-antidepressant-drugs/​

(2006) " Antidepressant Discontinuation Syndrome "

http://survivingantidepressants.org/index.php?/topic/823-2006-antidepressant-dis\

continuation-syndrome/​

Prolonged Withdrawal Syndrome

(2007) " Effects of Gradual Discontinuation of Selective Serotonin Reuptake

Inhibitors " :

http://survivingantidepressants.org/index.php?/topic/669-effects-of-gradual-disc\

ontinuation-of-selective-serotonin-reuptake-inhibitors-in-panic-disorder-with-ag\

oraphobia/​

(2006) " Persistent Tardive Rebound Panic Disorder, Rebound Anxiety, and

Insomnia " :

http://survivingantidepressants.org/index.php?/topic/779-2006-persistent-tardive\

-rebound-panic-disorder-rebound-anxiety-and-insomnia/​

(2006) From Dr. Shelton on " Prolonged Withdrawal Syndrome " :

http://survivingantidepressants.org/index.php?/topic/778-2006-from-dr-richard-sh\

elton-about-prolonged-withdrawal-syndrome/​

Neurobiology

(2003) " Neurobiology of Antidepressant Withdrawal " :

http://survivingantidepressants.org/index.php?/topic/671-2003-neurobiology-of-an\

tidepressant-withdrawal/​

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