Five misconceptions about antidepressants… and what science is doing to change them
Antidepressants are some of the most highly-prescribed yet misunderstood modern medicines, but how can scientific research debunk some of these common misconceptions…
Antidepressants are one of the most highly prescribed drugs in the world, with nearly 17% of adults in England being prescribed one last year (Public Health England, 2019). There are a number of antidepressants currently being used, with the most common know as selective serotonin reuptake inhibitors (SSRIs), including sertraline, fluoxetine (Prozac) and escitalopram.
In the last few decades, antidepressants have improved enormously in regards to their safety profiles and side effects, although there are still many issues that plague patients taking these drugs. There is also a lot of misinformation about antidepressants that only exacerbate the already highly-stigmatised condition. In the following sections, we’ll debunk some of these common misconceptions about antidepressants and how science is trying to overcome the underlying issues.
Misconception 1: Only depressed people take antidepressants
Antidepressants are a bit of a misnomer. While many people taking this class of psychiatric medication do have Major Depressive Disorder, they are also used to treat other medical conditions. For example, SSRIs are also used to treat anxiety disorders, bipolar disorder and PTSD. But the use of SSRIs goes beyond mental health conditions. SSRIs have also been trialled for the treatment for spinal cord injury — one of the hypnotised actions of antidepressants is to increase the plasticity of neuronal networks, so it is believed that giving SSRIs following spinal cord injury will help any surviving neurons to reform connections and promote functional recovery. This was demonstrated experimentally in rats given the SSRI fluoxetine which produced much greater functional recovery than those given a control substance (e.g. Scali et al., 2013).
Moreover, the serendipitous discovery of the antidepressant properties of a lot of these drugs means they’ve been used to treat other conditions for many years. For example, isoniazid was historically used to treat tuberculosis, but was subsequently repurposed following reports of its “euphoric effects”. Other antidepressants have also been used to treat Parkinson’s disease, and as depression is common in patients with dementia, many of these patients also take SSRIs.
Misconception 2: Antidepressants work for everyone
Although rates of depression are rising and the prescription of antidepressants are incredibly high, the efficacies of these drugs are worryingly low. In a systematic review of 21 antidepressants published in 2018, it was shown that only about 50% of patients will respond to an antidepressant or experience a long-term improvement to mood. Moreover, the placebo effect alone will produce improvements to depressive symptoms in up to 40% of patients, meaning the antidepressant itself only works in an additional 10% of patients (Cipriani et al., 2018). As a consequence, many thousands of patients are taking antidepressant where a placebo alone may have been beneficial, or that will simply may never help them.
Hence there is a drive to predict if a patient will respond to a drug in order to reduce the number of patients with whom initial antidepressant treatment is unsuccessful. In the past, baseline features such as a patient’s demographics or previous illness history were used to predict if they would respond to an antidepressant. Recently, analysis of changes to emotional bias and specific depressive symptoms in the early stages of treatment have been used, as these measures have been shown to be more predictive than baseline features alone (Browning et al., 2019). In an ongoing trial, patients undergoing standard antidepressant treatment are being compared to those that are swapping antidepressant treatment if after week there is no change to specific predictive psychological tests. (Clinicaltrials.gov, 2019). If successful, this advance could help more patients to respond to their treatments by reducing time wasted taking drugs that will never work for them.
Misconception 3: Antidepressants work immediately
Another common misconception about antidepressants is that they will instantly make you feel better. As implied from the section above, if it is necessary to predict if a patient will respond to an antidepressant even a week into their treatment, it is clear that antidepressants do not improve mood immediately. In fact, studies from the late 1990s suggest that for patients taking SSRIs it can take between 6–8 weeks for there to be a perceivable change in mood (Sechter et al., 1999). Although there is evidence that antidepressants change the way you think with even just one dose (for example, subjects given just one dose of an SSRI perceive neutral faces as more positive; Harmer et al., 2009), there is a substantial delay before any clinical improvement to depressive symptoms is seen.
While this is the case for the antidepressants currently in use, more recent discoveries suggest there could soon be antidepressants that work much faster. In 2011 a study found that single sub-psychomimetic dose of ketamine had an immediate antidepressant effect, which lasted for up to two weeks (Autry et al., 2011). Ketamine targets the glutamatergic system as opposed to the serotonergic system that is altered by SSRIs, suggesting this new approach could herald the way for the development of similar fast-acting antidepressants.
Misconception 4: Antidepressants are addictive
One of the most widespread misconceptions is that they are addictive. In order to address this issue, the definition of “addictive” must first be established. According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the most up-to-do descriptions and diagnostic criteria for all mental health disorders, true addiction must include a dependence on the drug being taken, as well as a compulsion to take it. Although patients may depend on antidepressants to maintain a stable mood and allow them to live a normal life, there is very little evidence that patients develop a compulsion to take these drugs. This is very different from addictive drugs such as opiates or benzodiazepines where people feel a need to seek out and take the drug they’re addicted to.
The lack of addictiveness of antidepressants was confirmed in a 2019 analysis by Public Health England that assessed a number of highly-addictive psychiatric drugs but noted that long-term antidepressant treatment is not associated with the development of an addiction. This can also be demonstrated in animal studies — for example, rodents given free access to addictive drugs such as opioids and benzodiazepines will gradually increase their intake over time, but this is not seen with treatment with antidepressants.
Nonetheless, although antidepressants are not considered addictive, a large number of patients coming off SSRIs do experience withdrawal symptoms. A recent meta-analysis found that over half of patients discontinuing an SSRI experience symptoms such as increased anxiety, sleep disturbances, nausea and dizziness, which can last for many months (Davies & Read, 2019). However, there is relatively little research into this condition or its neurobiological underpinning, hence a recent announcement from the Royal College of Psychiatrists called for the guidelines surrounding antidepressant treatment to be updated and for more research into the cause of these disabling withdrawal symptoms.
Misconception 5: Antidepressants are the only effective treatment for depression.
While antidepressants are the first-line treatment for depression, they are not the only solution. Counselling, technically known as cognitive behavioural therapy (CBT), is also recommended. CBT involves helping patients to relearn more positive associations in life to counteract the negative perceptual bias linked to the depression. This works in conjunction with the pharmacological antidepressant drugs that are thought to increase neuronal plasticity and therefore aid this relearning process.
Although CBT is much more difficult to access than antidepressant medication, it has been shown to decrease depressive symptoms (Hofmann et al., 2012). Moreover, the combination of antidepressants and CBT increases rates of response to treatment (Cuijpers et al., 2014), and therefore should be considered whenever treating a patient or predicting if they will respond to said treatment.
It is therefore clear that despite being so widely prescribed there are still a number of misconceptions about antidepressants that we need to continue to discuss in order to dispel. Moreover, more research is needed into why there is a delay in therapeutic action and the lack of efficacy of the currently-prescribed antidepressants, as well as the development of novel treatments that work faster and better to combat the ever-growing burden of depression in today’s society.
References
Autry et al. (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature, 475(7354): 91–5.
Browning et al. (2019) Predicting treatment response to antidepressant medication using changes in emotional processing. European Neuropsychopharmacology, 29:66–75.
Cipriani et al. (2018) Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet, 391, 10128: 1357–1366.
Clinicaltrials.gov (2019) Predicting Response to Depression Treatment (PReDicT). US National Library of Medicine. ClinicalTrials.gov Identifier: NCT02790970. Last updated January 2019. Available online: https://clinicaltrials.gov/ct2/show/NCT02790970.
Cuijpers et al. (2014) Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry, 13(1): 56–67.
Davies & Read (2019) A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addictive Behaviours, 97: 111–121.
Harmer et al. (2009) Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry, 166: 1178–84.
Hofmann et al. (2012) The Efficacy of Cognitive Behavioural Therapy: A Review of Meta-analyses. Cognit Ther Res., 36(5): 427–440.
Public Health England (2019) Dependence and withdrawal associated with some prescribed medicines: An evidence review. https://www.gov.uk/government/publications/prescribed-medicines-review-report
Scali et al. (2013) Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury. Scientific Reports, 2217.
Sechter et al. (1999) A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatient. Eur Psychiatry, 17: 1–8.
