It is hard to believe that a year has gone past since I posted Playing the Odds: Antidepressant Withdrawal and the Problem of Informed Consent. I want to thank all of you who reached out to me to through email, phone calls and office visits to share your thoughts and experiences with me. It was informative and enlightening, and bought to me a greater understanding of the problems related to long-term SSRI toxicity.
The feedback I received after posting ‘Shooting the Odds’ underscored the more controversial aspects of SSRI toxicity. Common themes concerned the abrupt onset of new symptoms 3 to 12 months after stopping the drug, reinstatement of the drug failing to help withdrawal related symptoms, the possibility that withdrawal-related symptoms can persist indefinitely and concerns about using benzodiazepines to help with tardive akathisia.
My patient population suggests that the problems relating to stopping SSRI antidepressants (which also includes SNRIs) must be widespread, and often severe. It used to be that people with these sorts of problems contacted me only because they were aware of my subspecialty interest in this area. Increasingly I am seeing patients who contact me for problems related to stopping a SSRI without knowing anything about me at all, because they found my name in their insurance plan provider list and I am nearby. This didn’t happen a few years ago. It appears that problems relating to stopping SSRIs are widespread and accelerating.
Since my last blog the patients whom I have seen and people I have spoken with reinforce the notion that withdrawal-related symptoms may show up abruptly months after stopping the drugs. I recently saw a patient who stopped an SSRI rapidly after a 15 year cumulative exposure. Surprisingly, there were no immediate withdrawal related symptoms at all. Despite feeling well, the patient wanted to know if they were in danger because there was no tapering and wondered if it would be safer to restart and then taper the drug
This was an interesting question. It appears that the immediate onset symptoms – zaps, vertigo, vivid dreams, flu like symptoms and mania, are somewhat different from the late onset symptoms which are collectively referred to as tardive akathisia. I have not, however, seen late-onset symptoms that present as zaps and vertigo. The immediate and late-onset withdrawal-related symptoms may have different mechanisms of action. While tapering clearly reduces the immediate onset symptoms, it is unknown whether tapering has any effect on the late onset symptoms. Besides this one patient, I have seen other patients who had no immediate withdrawal related symptoms and subsequently went on to develop late onset symptoms.
This particular patient did well for 4 months and then after their dog died, they had a very abrupt onset of a severe, almost intolerable depression which remitted when the drug was reinstated. When the patient first presented in the office, I could not see any benefit in reinstating and then tapering when the patient was already feeling well. Reinstating can sometimes be harmful. In retrospect I wonder if tapering could have been beneficial.
This illustrates another finding concerning the late-onset symptoms. While it is difficult to determine cause and effect, to some extent it appears that the late-onset symptoms are related to an excessive reaction to a stressor. Another patient had late onset symptoms of severe anxiety after a fairly mild earthquake. The patient commented to me that despite having been through earthquakes in the past, they had never had a fear of earthquakes before. It seemed out of proportion to the patient.
My experience is that reinstatement of the drug shortly after onset of late withdrawal symptoms works well. I typically reinstate slowly. It appears that the duration of drug use is unrelated to success of reinstatement. On the other hand, the longer the late onset withdrawal symptoms persist before reinstatement, the more likely it is that reinstatement is not going to help and may hurt. I have seen patients who suffered tardive akathisia for over a year, and then reinstated only to find that it made matters worse.
Recently I saw another patient, a 32 year-old person with a 7-year exposure to Celexa and Lexapro. We successfully tapered off of the drug and stopped it completely. They had minimal acute withdrawal symptoms, but had panic attacks at 7 months after stopping. The onset of the panic attacks coincided with an insurance company physical which disclosed high blood pressure and possible kidney problems. There was also severe ongoing generalized anxiety, racing thoughts, akathisia and insomnia organized around fear of kidney failure. They were prescribed Xanax 0.5 mg which was to be taken no more than twice a week to prevent dependency. The drug was taken infrequently and 30 tablets lasted for 7 months. By 14 months there were no further panic attacks, anxiety or akathisia and there were no panic attacks at follow up 24 months after stopping. The patient commented that they felt like their “life was starting” since stopping the drug, adding that deeper and more meaningful emotions and interpersonal relationships were experienced. This person also had sexual dysfunction for the entire 7 years of having taken the SSRI which resolved completely on cessation and resulted in a much better relationship with their partner.
This case illustrates a few notable features of stopping SSRIs. I wonder if the late-onset symptoms relate to overreaction to stress. The abnormal blood work preceded the anxiety as did the earthquake in the other patient. Also, it is notable that the late-onset symptoms went away over a few months. This suggests that, at least in some patients, the late-onset withdrawal symptoms may be transient. If possible, waiting it out instead of reinstating may be the best treatment option.
However, it is difficult to not reinstate the SSRI in patients with tardive akathisia. The suffering of these patients is far more severe than what I see in patients who have disabling anxiety or depression unrelated to SSRI use or withdrawal. These patients are often on the edge of suicide, partially from the discomfort of the akathisia, and partially from a sense of deep, hopeless depression.
Besides reinstating the SSRI, the benzodiazepines can offer significant relief from the akathisia. The most intense criticism of my last blog came from people who were opposed to the use of benzodiazepines. At the risk of eliciting the same, vehement criticism, it is my opinion that benzodiazepines are a useful tool in working with tardive akathisia. Medicine is filled with imperfect choices, and this is one of them. Of course, benzodiazepines are problematic, but for some people with tardive akathisia, they are literally life saving. In the above patient, we were able to use infrequent doses of Xanax with good symptomatic relief and no dependency. I have seen two patients who had severe akathisia and took benzodiazepines with benefit, and became dependent on them. Still, these two were able to taper and stop them without incident years later after akathisia stopped.
I have been profoundly influenced by a patient I saw who had a state of tardive akathisia that was so intolerable that they were extremely suicidal. Valium was prescribed and when the dose got up to 90 mg of Valium they calmed down and suicidal thoughts stopped. Two weeks later, out of concern about the high dose of Valium, I reduced it to 60 mg, and the akathisia came back and the patient committed suicide. The patients with tardive akathisia are pretty much all suicidal to various degrees, and the benefits of benzodiazepines need to be considered in certain patients.
In 2012 a then 56-year-old person contacted me wishing to stop taking Effexor (150 mg) after a 14-year exposure. The older a person is and the longer the drug has been taken, the less likely the person is to successfully taper off the SSRI. After reading ‘Informed Consent’ and learning about potential difficulties ahead, the patient still wanted to try stopping Effexor. The patient had run out of medication, at times, in the past and experienced a number of unpleasant withdrawal symptoms. It was the withdrawal symptoms that convinced the patient that the drug is toxic and that stopping it was essential. We used the bead tapering strategy, where 5% of the beads from a 150 mg capsule are removed per month until 75 mg was reached. At 75 mg the tapering schedule was changed to 2.5% per month. Some months when things were particularly stressful the patient elected not to decrease the dosage. We are at 54 mg and the tapering continues at this time. To date there have been almost no withdrawal related symptoms. We are optimistic at this point. This is a good experiment in ultra conservative tapering, and may answer some questions about the value of tapering ultra-slowly in preventing both acute and late onset withdrawal symptoms.
The question that I am most frequently asked is whether tardive akathisia ever goes away. The answer is an ambiguous ‘sometimes.’ The general rule is that if the condition is showing any improvement, then it is likely that the improvement will continue. Improvement is not linear, and usually goes two steps forward and one step backward. Still, if the general trend is towards improvement, then continued improvement is expected. Sometimes it improves quickly, and remits over a few weeks or months. I have also seen a few patients who improved steadily and almost (but not quite) to baseline over 5 to 7 years.
It is a lot more problematic if there is no improvement at all or if the withdrawal symptoms are severe. If akathisia is severe and impairing, it is not something that can be just watched over for months and years, and my approach is to reinstate early on in order to restore well-being and functioning. If it is milder and more tolerable, but there is no trend towards improvement, decision-making is more complex. How long do you wait before reinstating? The longer you wait the less likely reinstatement is to work. Usually the trend towards improvement can be seen within the first month or two, but this is not always easy to discern when the course is erratic. For the patient with milder tardive akathisia the direction is unclear, but intermittent benzodiazepine use becomes a viable option.
When patients request help with SSRI toxicity, I ask them why they didn’t go back to their prescribing doctor and ask them to stop the medicine. The typical answer is not surprising: the physicians are frequently unwilling to stop the medications at all or insist on substituting a similar medication or an antipsychotic medication. You would think that a high-functioning, more-or-less asymptomatic person asking to stop medications would find their physician agreeable. My guess is that physicians do not stop the SSRIs because the physicians have already had a few difficult experiences with what can happen after stopping the drugs. I suspect that physicians want to think that the problems are not withdrawal-related, but a reappearance of the mythical chemical imbalance or a new onset of bipolar disorder.
When you stop to think of how many patients the average family physician or psychiatrist puts on SSRIS, including themselves, family and friends, and the long-term results of these prescriptions, the cumulative misery effect is so large that if the physician really became educated, then they would be unable to live with themselves.
SSRIs have now been on the market for over 25 years, and some patients have been taking them for that long. So a lot of the patients seeking to stop taking SSRIs have been on them for so long that the risks from stopping the drugs are significant.
It is difficult to imagine anyone performing scientific study to prove that late neurotoxic withdrawal symptoms will occur. Ideally, a control group of people who recovered from anxiety/depression with no medications would need to be compared with a similar group who recovered with medication and then stopped the medication as well as another group who recovered with medication and never stopped taking the medication. I don’t see this on the horizon any time soon.
What is going to happen at 30 years or 40 years of cumulative exposure? Similar to global warming, it is the sheer magnitude of the problem that may prevent critical analysis. In the meantime, getting this information to the public, such as in well researched books like ‘Anatomy of an Epidemic’ and the excellent work from RxISK is the critical first step. A decade ago patients were almost always insisting on an SSRI, but now a lot of patients know somebody who took an SSRI and went downhill rapidly and they are more interested in other treatment options. Let us hope that public opinion trends further away from SSRIs and the unproven benefits from psychiatric drugs in general and that research will be done to clarify just what these drugs are doing and what can be done about the adverse effects.
