Antidepressants: A Hard Habit to Break?
The use of antidepressants in the treatment of depression and a number of other medical conditions is increasingly common. Millions of people in the U.S. alone (more than 13% of all Americans by recent estimates) take antidepressants. By far the most commonly prescribed antidepressants in the general population are selective serotonin reuptake inhibitors, or SSRIs, such as Prozac, Paxil, and Zoloft.
Studies have shown that these drugs can be effective in treating symptoms ME/CFS and fibromyalgia, even when patients are not suffering from depression. Medications that act on multiple neurotransmitters, such as venlafaxine (marketed under the brand name Effexor in the U.S.), have been found to be especially helpful in some patients. Given the lack of effective treatments for ME/CFS and fibromyalgia, antidepressants are often the first line of defense in addressing pain, unrefreshing sleep, “brain fog,” and other symptoms.
Many patients stay on these medications (or switch between several types or brands of antidepressants) for years at a time. However, a lot of patients may consider stopping treatment after a period of time, for a number of reasons. According to Joseph Glenmullen, author of The Antidepressant Solution: A Step-by-Step Guide to Safely Overcoming Antidepressant Withdrawal, Dependence, and ‘Addiction’, “People who want to try going off today’s antidepressants are usually either feeling better and believe they no longer need the drugs, or are having significant side effects.” Others may be concerned about risks associated with long-term use of antidepressants.
While some individuals will be able to discontinue their medication without noticeable difficulty, others are caught off guard when they experience new and distressing symptoms. These symptoms can range from fatigue and irritability to sensory abnormalities and cognitive difficulties. According to a 2005 Newsweek article, as many as 50 percent of people who stop using antidepressants will experience some symptoms of withdrawal.
Antidepressant Withdrawal: An Under-Recognized Problem
Despite the number of people affected, there has been little scientific study of the problem, and many physicians are unaware that for some patients, withdrawal reactions can be severe. In fact, some doctors are baffled when patients come into their offices reporting a wide range of symptoms that run the gamut from physical to psychiatric. Some practitioners may falsely attribute symptoms to ME/CFS or depression. Others may suspect the onset of a new illness, which can lead to unnecessary and costly tests or treatment.
Over the years, antidepressant manufacturers have played down or even denied the problem of withdrawal reactions. While they acknowledge that withdrawal effects are possible, they have claimed that they are rare or that they are usually mild and short-lived if they do occur.
However, many patients tell a different story. Even a cursory search online turns up scores of stories detailing moderate to severe withdrawal reactions. In addition to patient stories, a number of articles and websites can be found written by experts who have observed frequent withdrawal problems in their patients, some of them severe. Many of the resources offer useful guidelines on how to address withdrawal reactions.
While the manufacturers of major brands of antidepressants acknowledge the possibility of withdrawal symptoms in the fine print of their product inserts, they downplay these risks. According to Thomas J. Moore, author of the book Prescription for Disaster: Hidden Dangers in Your Medicine Cabinet, the manufacturers of SSRIs assert that withdrawal has not been systematically studied. However, Moore points out, “Few drug companies are likely to volunteer to pay for an expensive study that has a good chance of revealing a new drug hazard.” As a result, patients are left to rely primarily on anecdotal evidence, and they typically do not become aware of this evidence until they go searching for information after experiencing problems themselves.
Experts on antidepressant withdrawal have expressed concern that a substantial proportion of clinicians are uninformed about withdrawal reactions. Even doctors who are aware of the risk may not know how significant an impact such a reaction may have, and they typically don’t discuss potential withdrawal symptoms with their patients before prescribing antidepressants. The withdrawal process can be so challenging for some individuals that they have difficulty “sticking it out” for the weeks or months that withdrawal symptoms last. Some patients feel they have no alternative but to go back on the drug.
The ‘Addiction’ Controversy & Other Word Games
In his book, Glenmullen describes a patient who saw a television commercial for Paxil, which depicted tense, sad, anxious people who — after being treated with the antidepressant — are then shown blissfully engaging in a variety of activities with their families. The ad explicitly states “Paxil is non-habit forming.” The patient complained bitterly to Dr. Glenmullen, “How can they get away with that?…I’m sitting there unable to get off Paxil for months watching them advertise it as non-habit forming…” Indeed, patients who know nothing about potential withdrawal symptoms before beginning an antidepressant — and then experience distressing symptoms upon discontinuing treatment — often feel misled and resentful that they were not informed of the risks.
Compounding the problem is semantic confusion about terms like addiction, habit-forming, dependence, and withdrawal. There is controversy in the literature about what constitutes “dependence” or “addiction.” Physical dependence on a drug (needing a drug in order to function) is typically not sufficient to define addiction. Many drugs, including some blood pressure medications, do cause physical dependence in that withdrawal symptoms will occur if the drug is discontinued, but this is said to be different from the classic withdrawal syndrome associated with alcohol or barbiturates.
Moreover, antidepressants are not usually termed addictive because they are not linked to drug-seeking behavior and patients don’t develop tolerance — that is, they don’t need increasingly higher doses to achieve the same effect — nor do they exhibit the compulsive need or desire for the drug despite negative consequences, another defining characteristic of addiction.
To a patient trying to discontinue using an antidepressant and having difficulty doing so, however, these distinctions may seem inconsequential. An article in Drug & Therapeutics Bulletin suggested, “Debate about whether the ‘discontinuation’ syndrome is different from classical ‘withdrawal’ is probably largely a matter of semantics…From the patient’s point of view, however, discontinuation symptoms would be highly important if they resulted in any marked degree of difficulty in stopping the treatment, and might well feel tantamount to dependence.”
In fact, it may be that withdrawal symptoms have an even greater effect on ME/CFS or fibromyalgia sufferers than the general population, although no scientific study has explored this question. Since it is well-known that this group of patients tends to be sensitive to medications, it is quite possible that they would be particularly sensitive to discontinuation as well.
A New Name For An Unwelcome Problem
Antidepressant withdrawal began to come to the attention of doctors and patients in the mid-1990s. Over the following years, antidepressant manufacturers have adamantly denied that the drugs are addictive or habit forming. Once the issue began to receive increasing attention, the drug companies led a successful effort to adopt the term “antidepressant discontinuation syndrome,” in order to avoid association with the concept of addiction and withdrawal. This terminology is now used in the medical literature.
Withdrawal reactions are distinct from a recurrence of the original disorder.
Some experts argue that the pharmaceutical companies’ insistence that antidepressants are “non-habit forming” and their efforts to de-emphasize withdrawal effects have made it difficult for doctors and patients to get accurate information. However, there is reliable information available on the topic, which can be found if one searches for it.
Understanding Withdrawal Symptoms
Withdrawal or “discontinuation” symptoms may emerge when a drug is stopped abruptly, when doses are missed, or when the dosage amount is reduced. While the mechanism of action in antidepressant withdrawal symptoms is unknown, experts have proposed a variety of hypotheses. One theory is that the use of SSRIs over a period of time causes serotonin receptors in the brain to “down-regulate” due to the increase of serotonin available. When the SSRI is discontinued, the decrease in serotonin combined with the down regulation of the receptors causes a deficiency of serotonin, which in turn could cause a variety of symptoms.
Symptoms of antidepressant withdrawal include:
- Gastrointestinal disturbance (nausea, diarrhea, abdominal pain)
- Sleep problems (insomnia, vivid dreams)
- Fatigue, malaise, drowsiness
- Flu-like aches and pains
- Agitation, irritability, anxiety
- Depression, mood swings
- Confusion or cognitive difficulties
- Memory problems
- Dizziness/light headedness
- Sweats, chills
- Change in appetite
- Electric shock-like sensations
- Other strange, tingling, or painful sensations
- Muscle spasms, tremor
- Numbness, burning, or tingling
- Ringing or noises in the ears
While withdrawal symptoms vary a great deal between individuals, two important factors affecting the frequency and severity of withdrawal reactions seem to be the dosage and the length of time an antidepressant has been taken. Withdrawal symptoms may begin within days or even hours from the time of the last dose. Reports from patients who experienced withdrawal symptoms after missing a single dose are not uncommon. One patient remarked, “I’d feel a kind of electric jolt in my head and remember that I had forgotten to take my Effexor that day — it was like an alarm clock, reminding me to take my medication.”
It is important to note that some patients may have no symptoms associated with discontinuation of antidepressants. In milder cases, problems may peak after a few days and resolve within a week or two, but in others, symptoms can persist for weeks or months, and some individuals may find it very difficult to stop treatment.
Withdrawal reactions are distinct from a recurrence of the original disorder. For example, it is common for patients being treated for depression — upon stopping or reducing the dosage of the antidepressant — to mistake withdrawal symptoms for a return of their depression. However, withdrawal symptoms usually start within just a few days of stopping the antidepressant or reducing its dose, whereas depressive relapse tends to build up gradually over the course of several weeks or months.
This is important to keep in mind for ME/CFS and fibromyalgia patients, as it may also be true of other symptoms like pain and sleep problems. A sudden increase in these symptoms after stopping an antidepressant may indicate a withdrawal reaction, rather than a worsening of the original symptoms.
Different antidepressant drugs vary in their propensity to cause withdrawal symptoms. A key factor is the drug’s “half-life.” The term “half-life” is used to describe how quickly a drug is eliminated from the blood and is defined as the time it takes for the concentration of medication in the body to be reduced by one-half. Antidepressants with a long half-life (such as Prozac/fluoxetine, with a half-life of 4–6 days) tend to cause fewer withdrawal problems than drugs like Effexor/venlafaxine, which has a half-life of only about 5 hours. For example, it takes more than three weeks for 90 percent of the concentration of Prozac to be eliminated from the body. This provides a built-in tapering process, giving the brain cells more time to adjust. As a result, a much smaller percentage of people experience withdrawal symptoms with Prozac (only about 14%) than people do with Paxil (66%) or Effexor (78%).
Managing Antidepressant Withdrawal
Despite their claims that antidepressants are “non-habit forming,” the drugs’ manufacturers now warn against stopping antidepressants abruptly and suggest reducing the dosage gradually, though they provide no specific guidelines. The British National Formulary (otherwise known as the “doctor’s prescribing Bible” in Britain, which contains comprehensive information on prescription medications, including side effects, costs, etc.) recommends that patients who have been taking antidepressants for 8 weeks or more should taper off the medication over a 4-week period. Other experts suggest reducing the dosage by one-quarter every 4 to 6 weeks. Unfortunately, there has been little scientific study of various methods of discontinuation.
Clinical management of antidepressant withdrawal reactions can be handled in a number of ways. If symptoms are mild and tolerable for the patient, the syndrome can be allowed to “run its course.” Symptoms will usually abate within days or weeks for most people. However, some patients experience severe symptoms, or symptoms that worsen over the first several days or weeks. For these patients, the antidepressant can be restarted at its original dosage, which usually resolves symptoms within 24 hours. Then a more careful, methodical approach to drug withdrawal can be used, in order to keep symptoms at a tolerable level.
In The Antidepressant Solution, Glenmullen outlines a gradual tapering schedule that he says works for most patients. He points out, however, that deciding on the dosage reduction is really a process of trial and error because it’s impossible to know what kind of withdrawal reaction an individual will have. Following the initial reduction, it is essential to monitor any symptoms in order to determine the next step in the process. The goal is to have a mild withdrawal reaction or none at all and, thus, to be able to further reduce the dosage at regular intervals — roughly once a month — until the medication is stopped. Mild symptoms are those that are tolerated relatively easily and do not affect the patient’s ability to function.
If a patient has a moderate to severe withdrawal reaction, then the dosage reduction will need to be customized, making smaller and smaller reductions until symptoms are mild or non-existent. Even low doses of antidepressants may need to be tapered for some people because frequently these patients were prescribed low doses precisely because of their sensitivity to medication.
Dr. David Healy, MD, Director of the North Wales Department of Psychological Medicine and a prominent expert on antidepressants, agrees with Glenmullen and others that some individuals are extremely susceptible to withdrawal effects and may require very conservative tapering regimens. For those who have difficulty discontinuing antidepressants, Healy recommends a plan that involves converting the dose of the medication a patient is taking to an equivalent dose of Prozac, the rationale being that Prozac’s very long half-life will minimize withdrawal problems. After stabilizing on Prozac for at least a week, patients can begin reducing the dose by one-half, though an increase in symptoms may warrant reducing the dosage in smaller increments. If there are problems at any particular stage, Healy recommends that patients remain at that stage for a longer period of time before making further reductions.
Working with Your Doctor
It is vital for patients to be aware that antidepressants should not be stopped abruptly. If you are currently taking an antidepressant and are considering discontinuing treatment, it is critical that you complete the process under careful medical supervision. It is also a good idea for patients who are considering taking antidepressants (or switching to a different drug) to discuss with their doctors the potential problems of withdrawal and how they might be managed if they occur.
More research into antidepressant withdrawal is needed so that the extent of the challenge can be understood and evidence-based clinical recommendations can be developed. Understanding the possibility of withdrawal reactions and how to address them clinically does not preclude recognition of the beneficial effects that antidepressants have for many patients, including patients with ME/CFS or fibromyalgia. Antidepressant withdrawal is a concern that must be confronted openly and directly; with accurate information and good communication, the effects of withdrawal can be overcome.
Perhaps Dr. Glenmullen says it best: “Indeed, once patients are ready to go off antidepressants, tapering them over time provides a wonderful opportunity for collaboration, joint decision making, and strengthening the doctor-patient relationship that is at the heart of good medicine.”