5 things to know about antidepressants and discontinuation

While patients can easily obtain a prescription for antidepressants from their GP, stopping the medicines is not as simple. 

Australian Pharmacist delves into how antidepressants are prescribed and used, and new guidelines designed to overcome the difficulties of cessation.

1. Antidepressants are overprescribed

One in seven Australian adults take an antidepressant. Guidelines recommend people take antidepressants for 6–12 months for an episode of depression, yet on average Australians take antidepressants for at least 4 years. But many people take them for much longer.

Long-term use of antidepressants puts people at risk of adverse effects such as sleep disturbance, weight gain, fatigue, sexual dysfunction, gastrointestinal problems, emotional numbing, cognitive decline and increased risk of falls.  

So why are so many people taking antidepressants for so long?  

With long wait lists and prohibitive costs – even with Medicare rebates – it’s cheaper and faster to get a prescription than go to therapy. 

Drug company marketing combined with attempts to reduce stigma in mental health care has led many people to believe they have a chemical imbalance that needs to be corrected. But current evidence does not support this theory. 

While antidepressants are extremely effective for some people, this is not due to an underlying chemical issue – with long-term use rarely indicated.  

When people try to stop they experience withdrawal symptoms, which can be terrifying and debilitating.   

2. Current practice is letting patients down

There is often a ‘set and forget’ mentality when it comes to antidepressants. But long-term use leads to downregulation of serotonin receptors, making the medicines less effective over time and leaving people more prone to withdrawal symptoms when they stop. 

Most guidelines say that withdrawal symptoms (euphemistically referred to as ‘discontinuation symptoms’) are mild and last 1–2 weeks. But this does not reflect what many patients experience.  

Patients have reported feeling betrayed by health professionals who don’t warn them about the possibility of severe and persistent withdrawal symptoms, and when/how to safely stop taking antidepressants. 

Frustration and loss of trust can occur when patients seek advice about withdrawal symptoms, only to be dismissed due to lack of awareness. 

The WHO/UN in a new position paper on mental health and human rights have called for higher standards on informed consent regarding psychotropic drugs, including their right to discontinue treatment and support to do so https://t.co/p3HWo7slDO pic.twitter.com/jvB9J9aihS

— Mark Horowitz (@markhoro) October 23, 2023

When conducting research for TaperMate, for a mobile app I’m developing to help people safely taper their medications, I discovered a plethora of online forums and Facebook groups for people seeking peer support and advice due to lack of support from prescribers. 

The two largest support websites – Surviving Antidepressants and the Withdrawal Project receive over a million visitors per month combined.

While these networks are amazing resources, people should be able to get up-to-date evidence-based information from their healthcare professionals too. 

3. Change starts with better guidelines

The Maudsley Deprescribing Guidelines, published earlier this year, are the culmination of decades of research – bridging the gap between clinicians’ current knowledge and patient’s real-world experiences. 

The author, Dr Mark Horowitz, is a training psychiatrist with personal experience of severe antidepressant withdrawal and lack of research and guidelines on antidepressant tapering. 

The guidelines provide drug-specific step-by-step advice about safely reducing or stopping all commonly used antidepressants, benzodiazepines, gabapentinoids and Z-drugs. They also provide information about the need for patient-centred tapering and the pharmacological basis for the recommendations to help healthcare professionals understand what patients are experiencing.

4. Hyperbolic tapering is the future

Pharmacists are likely familiar with linear tapering, reducing by the same percentage or dosage at each interval. For example, reducing by 25% of the original dose every 2 weeks, or a set amount (e.g. 5 mg) every 2 weeks. 

However, there’s a hyperbolic relationship between dose and response due to saturation of receptors. So, dose reductions also need to follow this hyperbolic pattern to minimise withdrawal symptoms.   

The Maudsley Deprescribing Guidelines include the receptor occupancy % for each drug at specified doses, providing guidance to make each dose reduction an ‘even’ effect at target receptors rather than an even decrease in dose. 

Another approach, recommended widely in patient support forums, is decreasing by a set percentage (usually no more than 10% per month) of the current, rather than original dose. 

This creates smaller reductions to minimise withdrawal as the dose gets lower and the changes in receptor occupancy become more profound. 

The problem is, hyperbolic tapering requires increasingly smaller doses, which can be difficult to achieve using commercially available medicine strengths. 

With only one liquid antidepressant, escitalopram, available in Australia, this provides a perfect opportunity for compounding pharmacies to provide a (literal) solution. 

But if patients can’t afford compounded medicines or have a preference for the tablets/capsules they already use, pharmacists can use SHPA’s Don’t Rush to Crush guidelines to help patients create their own liquids in small doses for hyperbolic tapering.   

5. Identifying withdrawal versus relapse

It’s important for both health professionals and patients to be able to distinguish between withdrawal and relapse. 

Unfortunately, withdrawal is commonly misunderstood to be relapse, leading to increased doses or additional medicines being prescribed – leading to greater risk of harm and contributing to people feeling they need to be on medicines for life.  

The Maudsley Deprescribing Guidelines outlines four factors to look out for: 

• Time of onset. Withdrawal symptoms typically appear within hours or days of reducing or stopping a medication. Relapse usually takes weeks or months after stopping, depending on the characteristic cycles the person experiences their condition.  
• Duration. Withdrawal symptoms can last days, months, or sometimes even years. It’s not simply a matter of waiting for the medicine to be cleared from the body – withdrawal symptoms can persist until the receptors have returned to their homeostatic state. The duration of symptoms in a relapsed condition is variable but may fit into characteristic cycles for individuals.  
• Response to reinstatement. During withdrawal, improvement will be seen within hours or days – particularly if reinstatement occurs shortly after symptom onset. In relapse the response is typically delayed, with most medicines taking 2–6 weeks to take effect.  
• Distinctive symptoms. Some withdrawal symptoms are hard to distinguish from relapse. But others are distinctly physical such as dizziness, nausea, headaches, sweating, and muscle aches. If a patient experiences ‘brain zaps’, you could almost certainly assume they’re experiencing antidepressant withdrawal. Psychological symptoms are also common in withdrawal, but any symptoms not present in the underlying condition should be treated with suspicion. Sudden onset of a new psychiatric condition following cessation of a psychotropic medication is highly unlikely.