The Unhappy Side of Antidepressants

By Jeanene Swanson 06/03/14

SSRIs can aid in depression and recovery, but users also become dependent and there can be major withdrawal symptoms. So where's the healthy balance?

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Use of antidepressants in the US has skyrocketed in recent years, with one in ten people taking them. While depression is often misdiagnosed, the fact remains that more patients are demanding them and more physicians are prescribing them. The most commonly used antidepressants are SSRIs, or selective serotonin reuptake inhibitors.

Many people stop taking their antidepressants for a variety of different reasons. First, SSRIs have been shown not to work for mild cases of depression. Often, people will experience side effects, common ones being restlessness, nausea, sexual problems, and GI upset. Sometimes people who have taken an SSRI for a long time will become “immune” to its effects, and it stops working.

While it’s routine for doctors to advise patients about these things, it’s less common for a doctor to talk about the “withdrawal” effects associated with not only SSRIs, but with all antidepressant drugs and prescription psychiatric medications. Counseling patients about the possible discontinuation syndrome is imperative, especially for dual diagnosis addicts who are at risk for relapse of both depression and addiction.

Short-acting medications, such as paroxetine (Paxil) and venlafaxine (Effexor) are more likely to cause discontinuation symptoms than longer-acting medications, such as fluoxetine (Prozac).

Not “withdrawal,” but still unpleasant

Some statistics state that about half of patients taking SSRIs will experience “withdrawal” effects - over a million people. Sam Ball, President and CEO of CASAColumbia, estimates that number to be lower, at about 20 to 25 percent of patients. Medically speaking, this is not a true “withdrawal” and is instead referred to as SSRI discontinuation syndrome. Severe discontinuation symptoms, Ball says, “come for a minority of patients, particularly for those who abruptly stop taking [their antidepressants].”

As with any medication taken regularly, one's body adapts. Coming off the medication is going to require a recalibration period. However, SSRIs are not technically addictive. “It would be a misinterpretation to call it an addiction,” Ball says. “Physiologic dependence is really different from drug addiction. In drug addiction, you often times have that physiologic dependence, but you have other symptoms,” including craving and drug-seeking behavior. Confusing the issue puts addicts with depression at an even greater risk, especially when taking these medications could literally mean the difference between life and death.

Symptoms of SSRI discontinuation vary considerably among people due to individual differences. They also depend on how long a patient has been taking the medication, the choice of medication, and most importantly, how long the taper is. Abruptly stopping an antidepressant leads to the worst possible outcome; taking lower and lower doses on a weekly or monthly regimen, also called tapering, affords the best results.

According to the book, SSRI discontinuation symptoms include nausea, headache, dizziness, chills, body aches, paresthesia (tingling), insomnia, and electric shock-like sensations; psychological symptoms; and in rare cases, auditory and visual hallucinations, extrapyramidal symptoms (problems with movement), and mania/hypomania.

Go on a number of online forums, however, and you’ll find everything from benign to hellish, and short- to very long-term symptoms. A popular web site for SSRI discontinuation syndrome, called Surviving Antidepressants, offers peer support; the second most visited topic is how to quit, or taper, effectively. Says the administrator in an email, “There are hundreds of thousands of patient postings all over the Web about the difficulties of quitting psychiatric medication and benzos, even under a doctor’s supervision.” The administrator adds that there are dozens of sites like this, set up to help confused patients figure out how to best taper based on other people’s experiences.

Another site, Beyond Meds, talks about the particularly “harsh” withdrawal from lamotrigine (Lamictal), an anti-epileptic that is sometimes used as a mood stabilizer to treat bipolar disorder, or as an add-on drug to treat unresponsive major depressive disorder. Discontinuation symptoms of extreme mood changes, irritability bordering on rage, and a general feeling that you are “going crazy” seem to be common among those who do experience a severe syndrome. Larissa Mooney, director of the UCLA Addiction Medicine Clinic, makes no mention of the withdrawal, only that she has used lamotrigine successfully for the treatment of bipolar depression and to help prevent mood episodes in patients with bipolar disorder, and that she has “found that it is often well tolerated.” She adds: “Though you can read almost anything on the Internet, Lamictal is not associated with a classic “discontinuation syndrome” like the SSRIs/SNRIs. However, its dose should also be tapered rather than stopped abruptly.”

SNRIs, or serotonin–norepinephrine reuptake inhibitors, help keep both more serotonin and norepinephrine around in the brain.  The two most commonly prescribed ones are venlafaxine (Effexor) and duloxetine (Cymbalta). According to online groups, going off Effexor too quickly can cause horrible dreams.

All this being said, most symptoms are mild and short-lived. In the case of more severe symptoms, the antidepressant can simply be restarted, followed by more cautious tapering. “It really depends on the specific medication and the half-life of the medication,” Mooney says. “Short-acting medications, such as paroxetine (Paxil) and venlafaxine (Effexor) are more likely to cause discontinuation symptoms than longer-acting medications, such as fluoxetine (Prozac).” The syndrome is more common when medications are stopped abruptly or when the taper occurs too quickly, she adds; slowly tapering off medication helps to minimize the risk of these symptoms. Sometimes, substituting a short-acting antidepressant with a longer-acting one helps minimize symptoms, too.

Weighing the risks

For dual diagnosis addicts, it’s especially important to treat both the addiction and the depression. “I prescribe SSRIs for both depression and anxiety.” Mooney says. “If symptoms are mild, I will wait several weeks to see if they resolve on their own with ongoing sobriety. If the individual has had a history of clinically significant depression or anxiety in the past - even during prolonged periods of sobriety - this is another indication that symptoms are more likely to persist and medications may be helpful.”

Columbia’s Ball says that assessing priorities is key. The risks of not treating a mood disorder are far greater than the risks of SSRI discontinuation, owing to the fact of depression and substance dependence being the “toxic duo behind suicide,” he says. And, he adds, an unmanaged mood disorder keeps an addict in a state of constant risk of relapse.

“A rule of thumb is, any drug that changes the brain when you take it chronically can and will produce some type of withdrawal when you stop it,” says R. Andrew Chambers, director of the Laboratory for Translational Neuroscience of Dual Diagnosis & Development at the Indiana University School of Medicine. “The question is, how big of a deal is it? I think that the discontinuation syndrome from SSRIs is really pretty minor league stuff” compared to the risks associated with not treating the underlying depression or anxiety in addicts.

Is it real? 

There are a lot of unknowns when it comes to SSRI discontinuation syndrome, mainly because the symptoms overlap with other disorders. Often, people will stop their meds early due to bad side effects or because they don’t feel they’re working. In this case, the sufferer may experience a depression relapse, and confuse it with discontinuation symptoms.

Harvard Medical School has some helpful ways to tell the difference. Discontinuation symptoms emerge within days to weeks of stopping the medication or lowering the dose, whereas relapse symptoms develop later and more gradually. Discontinuation symptoms often include physical complaints that aren’t commonly found in depression, such as dizziness, flu-like symptoms, and abnormal sensations. Discontinuation symptoms disappear quickly if you take a dose of the antidepressant, while drug treatment of depression itself takes weeks to work. Discontinuation symptoms resolve as the body recalibrates, while recurrent depression continues and may get worse.

Sometimes, post-acute withdrawal symptoms (PAWS) from the former drug of abuse can linger and be misinterpreted as SSRI discontinuation. Sometimes the symptoms can be confused if the addict has relapsed and is using while still on the SSRI. Other factors that might not be reported come into play, too:  Are you drinking caffeine, or smoking cigarettes? Are you taking other prescription medications that may be interacting with your antidepressant?

And, some people may simply be more sensitive to any effect, whether side or discontinuation. “In my experience, people with anxiety are actually more aware of side effects,” Chambers says. “On the other hand, it’s quite the opposite with people with addiction or dual diagnosis. Actually, those folks are in some ways less concerned with side effects - they’re quite used to putting stuff in their bodies and not really caring.”

It’s also plausible that someone might inadvertently exaggerate discontinuation symptoms. “Some people may over-interpret minor symptoms, but then you also have a large group who seem to be incredibly insensitive to their own internal emotional states,” Ball says. Chambers says he’s never treated or had a colleague treat someone who has had “brain shocks,” so he’s skeptical that it is as common as people believe. “For the vast majority of people, [SSRI discontinuation syndrome] is so subtle that no one notices it,” he says. 

Long-term “withdrawal” effects

Most cases of discontinuation syndrome last between one and four weeks. However, up to about 15 percent of people have symptoms that persist for months. Paroxetine (Paxil) and venlafaxine (Effexor) seem to be particularly difficult to discontinue, with reports of prolonged withdrawal syndrome lasting over 18 months for paroxetine. 

Ball admits that these symptoms can be “disruptive,” and can last for “a year or more,” based on how fast one tapers. However, Chambers doesn’t believe it. “When people talk about the SSRIs changing the brain in some way, [and] you have some sort of prolonged withdrawal, I don’t buy that,” he says. “I think that it’s more likely that the underlying psychiatric [disorder] is going to linger a lot longer.”

Regardless of who “agrees” with what patients are feeling, all those interviewed acknowledged that prescribing doctors do need to have more conversations about possible discontinuation effects of SSRIs and other antidepressants. Mooney already practices this with her patients. “I discuss potential relapse triggers in the context of therapy, which include low mood, stress, anxiety, and physical discomfort,” she says. “By having this discussion and staying in close contact with patients should symptoms emerge, we can usually avoid or mitigate the majority of potential problems associated with antidepressant discontinuation.”

Additionally, there is more evidence that taper rates need to be lengthened, and dosages reduced uber-gradually compared to how they’re typically decreased now. In fact, recent data from narcoleptic patients using SSRIs suggest that antidepressant discontinuation lasts over three months, and that current taper rates are far too short.

Finally, more studies need to be done, not only on antidepressant discontinuation syndrome, but also the effects of long-term use of antidepressants on mental health outcomes. “A handful of studies is almost never enough to know anything,” Chambers says. The trick - beyond getting the NIH to fund these studies - will be recruiting big enough cohorts and designing tests that rule out the many confounding factors to teasing out the true effect of the antidepressant alone.

As a plastic organ, the brain is capable of adapting to significant change, and thank goodness for that. “Coming from a dual diagnosis perspective, in many ways, addictive drugs are far more capable of altering the brain than any of our treatment drugs; and yet even with those drugs, if someone quits using and stays abstinent, they can recover,” Chambers says. “If people achieve true sobriety and sustain that, they can recover.”

Jeanene Swanson is a regular contributor to The Fix. She last wrote about erasing your traumas and alcoholism and genetics.

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Jeanene Swanson is a science journalist who specializes in mental health and addiction. As a science writer with a background in biotechnology, she enjoys turning complex subjects into stories that everyone can understand—and apply to their lives. You can find Jeanene on Linkedin.