Antidepressant discontinuation syndrome: An underrecognised and rapidly escalating problem

Antidepressants are one of the most difficult classes of drug to get off, especially after long-term use. But there are ways to minimise the risk of antidepressant discontinuation syndrome.

As I’ve discussed in previous articles, antidepressants are now the most commonly prescribed class of drugs in Australia, with ten per cent of adult Australians currently taking some form of antidepressant.

Despite their lack of efficacy when compared to placebo and their laundry list of serious side effects (from sexual dysfunction to bone fractures to premature death – see 5 reasons to think twice before taking an antidepressant and Dying to feel better – long-term use of these medications is becoming increasingly common. Many of my clients have been on antidepressants for decades; some - horrifyingly - since their early to mid teens.

Yet very rarely are patients warned that the longer they stay on these drugs, the more physically dependent on them they will become, and the higher will be their risk of the distressing (and potentially deadly) cluster of symptoms dubbed ‘antidepressant discontinuation syndrome’ or ADS.

An article published in the March 2020 edition of The Journal of the American Osteopathic Association shed some much-needed light on this badly neglected topic. (N.B. In the US, osteopathic physicians undergo exactly the same training as medical doctors before specialising in osteopathic medicine, and are licensed to practise as physicians.)

The article, titled ‘Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem’, points out that although “the mechanisms underlying the therapeutic effects and discontinuation symptoms of antidepressants are not fully understood” (in other words, no one really knows how they ‘work’), these drugs are increasingly widely prescribed not just for depression but numerous other conditions including obsessive-compulsive disorders, generalised anxiety disorders, eating disorders, and neuropathic and chronic pain syndromes, frequently resulting in long-term use.

The authors also highlight the tendency of doctors to assume that if most of their peers and colleagues prescribe a particular treatment, it must be effective and safe:

“Given the widespread use of antidepressants, physicians may be driven by an overestimated consideration of potential benefits, while appraisal of adverse effects are, by comparison, often overlooked.”

Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem

Antidepressant medications of all classes interfere with the activity of neurotransmitters – chemicals that neurons (nerve cells) use to ‘talk’ to each other, and to other target cells including muscles and glands.

For example, monoamine oxidase inhibitors (MAOIs), the oldest class of antidepressant, interfere with the metabolic breakdown of the neurotransmitters dopamine, noradrenaline and serotonin. These drugs are now rarely prescribed due to their suite of serious side effects and interactions with certain foods and other medicines; only two, Nardil and Parnate, are available in Australia.

Tricyclics (including amitriptyline, clomipramine, desipramine, doxepin, imipramine and nortriptyline) were the next class of antidepressants to be developed. They increase the availability of serotonin and norepinephrine by inhibiting their reuptake, as do the newer class of serotonin-norepinephrine reuptake inhibitor drugs (SNRIs) including venlafaxine (Efexor), desvenlafaxine (Pristiq) and duloxetine (Cymbalta).

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft), as their name implies, only interfere with the reuptake of serotonin.

Buprion (Wellbutrin, Zyban) inhibits reuptake of norepinephrine and dopamine.

Mirtazapine (Remeron) acts directly on serotonin and noradrenaline receptors.

The higher neurotransmitter signalling generated by all classes of antidepressants prompts essentially the same set of adaptations in the brain: altered production of neurotransmitters and the density of their receptors, altered signalling cascades associated with these receptors, and increased neuroplasticity in the limbic system.

In other words, the brain fights the biochemical effects that antidepressants exert on its activity by attempting to restore normal neurotransmitter activity. Over time, this creates physical dependence in much the same way that the body’s adaptation to chronic use of any neurotoxic substance, including alcohol and illicit drugs, induces dependence.

Unfortunately, the brain’s adaptation to antidepressant-induced interference with its function can lead to the severe and distressing symptoms collectively known as antidepressant discontinuation syndrome (ADS) if a person abruptly stops taking their medication, or sharply drops their dose. The sudden drop in neurotransmitter activity causes six key ADS symptoms, known by the mnemonic FINISH:

• Flulike symptoms

• Insomnia

• Nausea

• Imbalance

• Sensory disturbances (including electric shock-like sensations dubbed ‘brain zaps’)

• Hyperarousal (anxiety, irritability, impaired concentration, hypervigilance, excessive startle reflex).

Headache, lethargy, and low mood are also features of ADS.

All these symptoms begin within days of either large dosage reductions or sudden cessation of antidepressant use.

Additional discontinuation symptoms are associated with particular antidepressant classes. For example:

• Abrupt withdrawal from MAOIs may induce aggression, catatonia, cognitive impairment, and psychosis;

• Profound balance problems and Parkinson’s-like symptoms can occur after stopping tricyclic antidepressants; and

• Abdominal pain and diarrhoea are more likely after SSRI cessation.

The authors’ observation that withdrawal from SNRIs is associated with more severe ADS than SSRI withdrawal, accords with my clinical experience. Clients who have been taking Efexor seem to have a particularly rough time getting off it, and I have seen several clients who developed pronounced suicidal ideation (thinking about killing themselves and making plans to do it, and in one case, attempting suicide) when they attempted to reduce their dosage more rapidly than I advised.

The authors note that the longer a person has been taking an antidepressant, the higher the risk of ADS and the more important a gradual reduction in dosage rather than abrupt discontinuation becomes.

The authors provide a tapering schedule for each class of antidepressant, with the most gradual reduction schedule reserved for MAOIs and tricyclics.

However, my clinical experience leads me to endorse a slower tapering schedule than that proposed in the article for all types of antidepressants, particularly SNRIs.

I’m especially cautious with clients who have been taking antidepressants for many years, and those whose previous attempts to get off their medications have been unsuccessful.

While I’m deeply concerned about the long-term adverse consequences of antidepressant use, I’m even more concerned by the prospect of a client ‘crashing’ and (wrongly) concluding that they have no other option than to go back on medication.

Hence, I recommend deferring antidepressant withdrawal until my clients have built a strong foundation of habits that support their physical and mental health, as follows:

1. Adopt a nutrient-dense wholefood diet, with the majority of calories coming from whole or minimally-processed plant foods. In particular, a high intake of fruits and vegetables has been associated in numerous studies with improved mood and reduced risk of depression (see Good mood food and Want to feel happier? Change what’s on your plate!). Refined sugars and starches, and ultraprocessed foods must be minimised, and preferably eliminated.

2. Establish a daily exercise habit, preferably incorporating a variety of cardio, resistance and flexibility-building activities that you find enjoyable. Exercise is well known to improve mood and relieve anxiety (see 5 surprising benefits of exercise you never knew about).

3. Ensure that you are getting at least 7.5 hours of sleep per night, and maintain a regular bedtime and waking time. Insomnia, poor sleep hygiene and circadian rhythm disruptions (such as staying up late and then sleeping in) should all be addressed before starting an antidepressant taper as pre-existing sleep issues are likely to be exacerbated by drug withdrawal. Furthermore, there is a bidirectional relationship between sleep disruption, and anxiety and depression. Sorting out your sleep will help buffer you against relapsing as you wean off medication.

4. Develop a daily practice of downshifting. Mindful forms of exercise such as yoga, tai chi or qigong; prayer; journalling; and meditation are all options to explore. Many community health centres offer free or low-cost meditation, yoga and tai chi classes. Or you can choose from a plethora of mindfulness and meditation apps. I particularly recommend the Unwinding Anxiety app which has been a godsend for many of my clients.  

Once my clients are well-established in these habits, I advise them to find a doctor who will support their attempt to get off their antidepressant by providing prescriptions that allow a slow taper. I generally recommend reducing the dose by ten per cent every two to four weeks. This slow taper allows the brain to recalibrate to each dosage reduction before commencing the next one, minimising the risk of ADS. People who have been taking antidepressants for less than a year can often proceed faster than this; those who have been on any of these drugs for many years may need to take it even slower.

This tapering schedule usually requires prescriptions for several different dosages of the drug which can be combined in various ways. Liquid formulations of some antidepressant drugs are available, and these make precise dosage reductions much easier to manage. A compounding pharmacist can custom-make pills with the dosage prescribed by the doctor who is supervising your medication taper.

For antidepressants with a longer half-life, such as fluoxetine (Prozac), tapering can be done by skipping one dose every ten days, then one dose every nine days, eight days, and so on.

If ADS symptoms are encountered, the taper should be slowed down further; if symptoms are severe, revert to the previous dose until symptoms abate and then resume the taper by reducing the dose more gradually; for example by five per cent rather than ten per cent.

I strongly advise my clients to let trusted family members and friends know that they’re commencing a medication taper, and to educate them about ADS. All too often, concerned partners or family members (not to mention doctors who are, on the whole, poorly educated about the syndrome) will assume that the appearance of ADS symptoms is an indicator that the patient 'needs' an antidepressant to function normally, and should go straight back on the drug and never attempt to discontinue it in future.

However, once educated about the reality of ADS, loved ones can provide much-needed reassurance, and both practical and moral support for the healthful eating, exercise, sleep and stress-buffering habits that will aid successful withdrawal from the medication. In the case of severe or protracted symptoms, loved ones can also seek input from a well-informed health professional.

Besides the article mentioned above, there are a few excellent resources that I recommend to people who wish to get off antidepressants:

• Psychiatric Drug Withdrawal by Dr Peter Breggin. This title is quite expensive, so check whether your local library has it, or can obtain it for you.

• Mental Health Survival Kit and Withdrawal from Psychiatric Drugs by Dr Peter Gøtzsche. Well worth buying, but you can also read it for free in serialised form on Robert Whitaker's website, MadinAmerica.com, which is a veritable treasure-trove of information on the psychiatric industrial complex.

• Coming off psychiatric drugs: Successful withdrawal from neuroleptics, antidepressants, lithium, carbamazepine and tranquilizers by Peter Lehmann (editor). This book is a compilation of stories and articles written by people who have successfully discontinued psychiatric medications, and the health professionals who have developed expertise in helping them. You can read it for free on Archive.org.

To sum up, antidepressant discontinuation syndrome is real, common, and can be extremely distressing and frightening. The risk increases the longer a person stays on an antidepressant, and the more abruptly they try to get off it. Putting healthy lifestyle behaviours - nutritious diet, daily exercise, regular sleep and daily meditation - in place before attempting to get off antidepressants helps one cope with ADS symptoms if they occur and also helps to prevent depression and anxiety from recurring, while slowly tapering the dose reduces the risk that such symptoms will occur at all.

For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.