Depression is a prevalent and yet undertreated disease due to its associated stigma. Many sufferers decided to tough it up instead of talking about it, as most people do not respond well to this topic. As the emotion gets bottled up, depression may lead to self-harm and suicidal thoughts. Here in this article, we will talk about the class of medicine that we often neglect in our daily practices as health professionals – antidepressants and the proper use of them.

There are three major classes of antidepressants, namely SSRI, SNRI and TCA. Other antidepressants are newer (except moclobemide) and have less data regarding their uses.

1. Selective serotonin reuptake inhibitors (SSRIs)
   – Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
2. Serotonin and noradrenaline reuptake inhibitors (SNRIs)
   – Desvenlafaxine, duloxetine, velafaxine
3. Tricyclic antidepressants (TCA)
   – Amitriptyline, nortriptyline, dosulepin, doxepin, clomipramine, imipramine
4. Tetracyclic antidepressants 
   – Mianserine, mirtazapine
5. Other antidepressants 
   – Agomelatine, vortioxetine, moclobemide, reboxetine

Aside from efficacy, the choices of antidepressant initiated should be individualised, based on the side effect profile of the antidepressant chosen and comorbidities the patient has, to ensure quality use of medicine.

Serotonin syndrome – When the amount of serotonin reaches a toxic level

We know little about this in Malaysia, as antidepressants are not widely prescribed. Serotonin syndrome arises when a combination of agents that increases serotonin concentration in the body is used, leading to symptoms such as:

• Motor: hyperreflexia, clonus, tremor, incoordination, rigidity^1,2
• Mental state changes: anxiety, restlessness, confusion, hypomania, agitation^1,2
• Hyperthermia: shivering, sweating, fever^1,2
• Gastrointestinal: vomiting and diarrhoea^1,2

The mainstay of treatment is supportive, and all serotonergic agents should be stopped.⁵ Some examples of serotonergic agents include:

^1,2

If serotonin syndrome worsens, cyproheptadine, a sedative antihistamine, may be administered to reverse the serotonergic effects.^1,2

Cross-tapering and Withdrawal effects

Antidepressants with long half-lives will have fewer withdrawal effects.³ However, a more extended period of cross-tapering will be needed to avoid serotonin toxicity.

• Long half-life: Fluoxetine and vortioxetine^1,5,6
  At least two weeks of washout period is required to minimise the risk. Fluoxetine may require five weeks of washout.
• Intermediate half-life: TCAs, SSRIs (except fluoxetine), mianserin, mirtazapine^1,5,6
  Reduce the dose by 25% daily; a 2-4 days waiting period should render the serotonin level low enough to start another antidepressant.
  Common discontinuation symptoms in SSRIs include flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances and hyperarousal (FINISH acronym).³
• Short half-life: agomelatine, moclobemide, reboxetine, SNRIs^1,5,6
  SNRIs should be withdrawn gradually to prevent withdrawal symptoms. Withdrawal symptoms are rare in agomelatine, moclobemide and reboxetine. Wait for 1–2 days before starting the next antidepressant. However, agomelatine can be started immediately if one is to switch from an SSRI or SNRI.

Epilogue

The topic of depressive conditions should never be taboo. We all hit our lows at some point in our lives. As health professionals, we have an extra role of ensuring the antidepressive pharmacological therapies are safe, besides acting as supportive companions to the people who suffer from this condition. Remember, psychosocial interventions and psychotherapy are the first lines for busting depression.³ Some examples are peer intervention, exercises, relaxation, psychospiritual intervention, cognitive behavioural therapy, marital therapy, and interpersonal and problem-solving therapy.³ For the pharmacists out there who are interested in this subject matter, the Malaysian Mental Health Association (MMHA) group provides mental health first aid courses that train participants to resolve a mental health crisis.⁶

Let’s be part of the green ribbon group today!

References:

1. Australian Medicines Handbook 2020 (online). Adelaide: Australian Medicines Handbook Pty Ltd; 2020 July. Major Depression; [updated 2022 Jan; cited 2022 Jun 26]. Available from: https://amhonline.amh.net.au/
2. Boyer EW. Serotonin Syndrome (Serotonin Toxicity) [Internet]. WA: UpToDate; [updated 2023 Feb 16; cited 2023 May 15]. Available from: https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity?search=serotonin%20syndrome&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
3. Clinical Practice Guideline. Management of Depression [Internet]. Putrajaya: Malaysia Health Technology Assessment Section (MaHTAS), Malaysia; 2019. Available from: https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Psychiatry%20&%20Mental%20health/CPG_Management_of_MDD_(Second_Edition)_04092020.pdf
4. Hirsch M and Birnbaum RJ. Discontinuing antidepressant medications in adults [Internet]. WA: UpToDate; [updated 2022 oct 21; cited 2023 May 15]. Available from: https://www.uptodate.com/contents/discontinuing-antidepressant-medications-in-adults?search=switching%20antidepressants&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
5. Hirsch M and Birnbaum RJ. Switching antidepressant medications in adults [Internet]. WA: UpToDate; [updated 2022 Oct 20; cited 2023 May 15]. Available from: https://www.uptodate.com/contents/switching-antidepressant-medications-in-adults?search=switching%20antidepressants&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
6. Malaysia Mental Health Association. Mental Health First Aid (MHFA) Training [Internet]. Available from: https://mmha.org.my/education-training#mental-health-first-aid-course
7. Toth N. Picture available from: https://unsplash.com/photos/exI3uXWZgwo?utm_source=unsplash&utm_medium=referral&utm_content=creditShareLink