Quit Paxil, And Then…

… Zap!

Paxil, the world’s best-selling antidepressant, has become the target of growing complaints that stopping the drug causes severe side effects ranging from flu-like symptoms to electric-shock-like sensations in the brain that patients have labeled the “zaps.” This marks the first time that one of the new generation of antidepressant medications, often described as non-habit-forming, has been accused of being addictive.

The patient complaints, which previously circulated chiefly on electronic bulletin boards and specialized Web sites, became more public last week when a federal judge in California ordered the drug’s maker, GlaxoSmithKline, to pull TV ads that boast the drug is “not habit-forming.” The judge later put that ruling, which said the ads may have underplayed the drug’s possible role in causing withdrawal symptoms, on hold. Washington Post

This is a fascinating and far from clearcut controversy. There is no disagreement between the drug’s critics and defenders about whether the discontinuation symptoms exist, but a war of words about what to call them (and to some extent a dispute, in which I side with the unfortunate users, about how severe and uncomfortable the discontinuation symptoms are). The gist of the manufacturer’s argument is that ‘discontinuation symptoms’ are different from ‘withdrawal’ and ‘addictiveness’, that there are other classes of medication whose abrupt discontinuation causes medical symptoms which we do not call addictive — e.g. steroids or certain blood pressure medications. The Food and Drug Administration sides with them in these objections.

As critical psychiatrist Joseph Glenmullen (who was a former trainee of mine with whom I usually disagree, and whose book Prozac Backlash I have dismissed in these pages as overblown grandstanding) says, ‘dependency’ arises when the cells of the body “were making adaptation to living with the drug 24 hours a day”. ‘Withdrawal’ is the body’s reaction to suddenly missing the drug once it has become so adapted to having it around. While a hard-and-fast mind-body distinction is no longer easy to make without backsliding to an archaic dualistic position, we usually reserve the term ‘withdrawal’ for those drugs whose discontinuation syndrome has a subjective component of mental distress (so Glaxo’s comparison with beta blocker antihypertensives, whose ‘discontinuation syndrome’ is rebound hypertension, is a specious one…).

So any class of medication taken on a consistent maintenance basis, which produces a physiological adaptation to having it around in the body, fits the bill as ‘dependency-inducing.’ From among dependency-inducing classes of medication, it is the medications in that class that exit the body rapidly on abrupt cessation of use that provoke withdrawal reactions. Hence Paxil, but not Prozac or Zoloft, among SSRI antidepressants; Xanax or alcohol but not Librium, Ativan, Klonopin or Valium from among the sedatives (surprised at my lumping alcohol in there? It is ‘cross-tolerant’ with the class of sedative anti-anxiety medications, called benzodiazepines, to which these others belong, acting on the same pathways in the brain…) ; heroin, morphine, oxycodone etc. but not methadone or buprenorphine among the opiate painkillers… The more-slowly-eliminated medications in each class allow the body to “de-adapt” gradually to their falling concentrations after cessation of use; they ‘self-taper’ after stopped. In fact, we usually treat dependency on a medication with the substitution of a longer-acting ‘cross-tolerant’ drug in the same class, e.g. methadone detox from heroin dependency, Librium or Ativan detox from alcohol dependency, Klonopin detox from Xanax dependency, etc. The substitution of the longer-acting drug, and its slow taper, will let the body down more easily and mitigate if not eliminate the withdrawal or discontinuation reaction. (This raises the question of whether it would be easier for people to stop Paxil by substituting one of the other, more slowly eliminated, SSRIs, and then tapering that instead, over the ensuing 5-10 days.).

But we usually mean something more than physiological dependency, and the potential to cause physiological withdrawal upon discontinuation, when we call a medication ‘addictive’ or habit-forming’ . These are certainly button-pushing words in our social context, and I believe it was proper for the judge to stay his own ruling to ponder this further. An addictive drug is one which produces a psychological as well as a physiological dependency; whose cessation induces cravings for renewed use as well as withdrawal symptoms; whose self-administration is reinforced by the positive subjective state each dose induces; and seeking and administering which comes to assume a disproportionate role in the user’s psyche, behavior and lifestyle. Addictive drugs are are also ‘abusable’, i.e. used recreationally rather than merely therapeutically, and often in escalating doses. This latter has both a physiological component — because dependency-inducing drugs also induce physiological tolerance to their effects — and a psychological one, to obtain a more extreme or more long-lived alteration. I think it is clear that Paxil — or SSRIs, from this point of view — should not properly be called ‘addictive’ in an sense similar to the opiates, alcohol, or the benzodiazepines. While psychological dependency — especially in the sense of ‘cosmetic psychopharmacology’, the term coined by Peter Kramer in Listening to Prozac to describe the potential of this class of drugs to improve temperament even in the absence of frank depression or any of the other indications for which the SSRIs are used — occurs, Paxil-seeking does not dominate anyone’s lifestyle, there is no street trade in the drug, taking a single dose is not mood-altering or euphoriant and thus not self-reinforcing, there are no temptations to escalate dose to intensify the experience and no cravings after stopping its use.

What is at stake if such a loaded word as ‘addictive’ is implied, I believe imprecisely and improperly, to the SSRIs? I certainly don’t care about protecting Glaxo’s market share or cash flow, but I do worry about needless restrictions on the efficacy or accessibility of my pharmacopoeia. Even long before concerns about Paxil became known, the first question patients to whom I have proposed an antidepressant often ask me is whether it is “addictive.” Furthermore, even drugs which assuredly are addictive in one setting — the street — can be used under medical supervision in a controlled way that does not promote or provoke abuse, dependency or withdrawal. Narcotic analgesics are the perfect example. Seriously distressed people who could benefit from or even require an SSRI for their relief or recovery may be needlessly dissuaded from its use by such concerns.

Whether we call SSRIs addictive or not, and I hope I have made it clear I think we should not, avoidance of this and other complications of their use requires skillful prescribing and attentiveness. As usual, I argue that many of the complications of psychotropic medication use, especially SSRIs, arise from marketing pressures which have led to these medications being prescribed by internists, primary care doctors and doctors in other, non-psychiatric, specialties who do not have the expertise or time to manage patients on these drugs with the care they deserve.

In the interest of conceptual precision, we should avoid loaded buzzwords whose main use is to manipulate popular misconceptions to fill the pockets of ‘ambulance-chasing’ law firms…

A Rebel Psychiatrist Calls Out to His Profession

“Dr. J. Allan Hobson, a psychiatrist for more than 40 years, is upset with his profession, saying it has lost its way. In a series of books, he has been trying to shake it up …”

Q. How would you reorganize medical training so that you’d attract better and more students to your speciality?

A. I’d tell them that they have a chance to work on one of the last great medical frontiers, which psychiatry could be. This is a field where they’ll have license to talk about psychology and physiology and philosophy, all together. Where else can you do that? NY Times