Dana Ayebare ’27
Mahmood, Raqeeb & Wallace, Vuokko & Wiles, Nicola & Kessler, David & Button, Katherine & Fairchild, Graeme. (2024). The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study. Health Expectations. 27. 10.1111/hex.13966.
Introduction
Antidepressants are increasing in use and cultural relevance in the West. After the onset of the COVID-19 pandemic, the rate of antidepressant prescriptions to teens and young adults in the United States increased by 63.5% (Chua et al., 2024). In England, the number of people with these prescriptions nearly doubled to 8.6 million between 2011 and 2022-23 (Thomas, 2023).
One often neglected aspect of medicating depression is withdrawal. Raqeeb Mahmood et al. explore this nuance in the article The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study, published in January 2024. The SSRI class of antidepressants is commonly prescribed in the treatment of major depressive disorder. Neuropsychologically, SSRIs work to increase the levels of serotonin—a chemical thought to help mood stability in the brain (Bamalan et al., 2024). SSRIs increase serotonin interactions with its receptors, which are present throughout the brain and spinal cord. This activity is relevant because serotonin receptors play a role in aggression, anxiety, appetite, cognition, learning, memory, mood, sleep, and thermoregulation, among other aspects of functioning (Wang et al., 2019). Withdrawal from SSRIs can induce a myriad of social, psychological, emotional, and cognitive changes.
In this article, Mahmood and his collaborators, from the University of Bath and the University of Bristol in the United Kingdom, employed qualitative methods to investigate these effects. Specifically, they conducted interviews with people who had made an attempt to withdraw from SSRI medication(s), regardless of whether or not they were taking medication at the time the study was conducted. The authors affirm that while previous research has had a narrow focus on the physical side effects of antidepressant withdrawal, their research methods introduce novel and necessary depth to this conventional knowledge. The aim of the study was to “aid clinicians on how to guide patients through [withdrawal]” (p. 1).
Participants and Methodology
Mahmood et al. sampled twenty people who had attempted withdrawal or completely withdrawn from SSRI antidepressants within a year of the study (p. 3). They had an average age of 23.5 years old. Of the twenty participants, 75% were women, and 80% identified as white. Students made up 85% of the sample, and 55% were in a non-cohabiting relationship. Only one (5%) of the participants identified as Black, two (10%) identified as Asian, and one identified as mixed race. Using the Patient Health Questionnaire (PHQ-9), a standard diagnostically reliable and valid assessment for depression (American Psychological Association, 2020), the researchers found that at the time of the study, 50% of the participants had moderate to moderately severe depression. At the time of the study, 55% of participants were actively taking SSRIs.
70% of participants tapered (progressively decreased) their withdrawal process for a more stable transition, and the same proportion self-reported recurrence of depression after withdrawal. At the time of their withdrawal attempt, 55% were on sertraline and 30% were on Prozac. These numbers are unsurprising, considering that those two medications are among the most commonly prescribed SSRIs (Marasine et al., 2021). Prozac is unique in that it is associated with the lowest incidence of negative withdrawal symptoms (Gabriel and Sharma, 2017), so arguably, the experiences of the participants withdrawing from Prozac would be optimal among this population.
In emphasizing the value of antidepressant users’ lived experiences with withdrawal, the authors aimed to be inclusive with their methods. They employed Patient and Public Involvement (PPI) to inform participant recruitment and a topic guide for the interviews. This involved meeting with eight individuals (from outside the study) who had experienced antidepressant withdrawal. They gained insight into general practitioner (GP) involvement in the withdrawal process, family relationships, and mood and thinking changes, all of which later proved to be meaningful in their findings. They used inductive reflexive thematic analysis, i.e. to generate individual and broad meanings from the interview data, as opposed to applying existing frameworks. A characteristic of thematic analysis is the labeling and organization of relevant elements of the data, or coding. The researchers generated semantic and latent codes—the former being the overt information that was given by the participants, and the latter being the implicit patterns and concepts that the researchers interpreted from the body of responses. The codes were combined into shared meanings and consolidated into themes. The authors created thematic maps to connect the final themes and subthemes, with quotes to represent each.
Results
Theme 1: ‘Double‐edged sword’ of emotional and cognitive impact
Upon withdrawal, most of the participants experienced release from emotional blunting—the suppression of emotions associated with antidepressant use. The “double-edged sword” in that is the subsequent heightening of emotions, memory recall, and thoughts, all negative and positive. The quotations that the authors chose to frame the theme mostly highlight the challenges of emotional and cognitive release, which could reflect a bias among the authors in favor of emotional blunting.
Theme 2: Negative social impact and engagement with others
Social detachment during the withdrawal process was common among the participants. Managing both withdrawal and social responsibilities was overwhelming.
Theme 3: Influence on physical health
In a change of tone, the authors cite the positive impacts that withdrawal had on the physical health of some of the participants. For this, it is relevant to note that antidepressants are linked to weight gain via increased appetite, especially citalopram and paroxetine (Anekwe, 2022), which 15% of the participants were taking at the time of withdrawal. Another common positive impact was increased exercise in order to manage mental health. This newfound sense of initiative could develop from the removal of the emotional stability, blunted or not, that medications may provide.
Theme 4: Extent of support during withdrawal
Along with the researchers, the participants emphasized the importance of support systems being informed about withdrawal, especially their GPs. Many found that people in their personal lives as well as their GPs were lacking in mental health literacy, which is “knowledge and beliefs about mental disorders which aid their recognition, management or prevention” (Sampaio et al., 2022). More specifically, the participants tended to bear the responsibility of regulating withdrawal by themselves.
Theme 5: Timeframe and flexibility in withdrawal is key
The framing of Theme 5 via participant quotes deviates from the others. In lieu of reported lack of support from clinicians, the participants took on an advising role to others seeking withdrawal. They advocated for planned but flexible tapering.
Conclusion
SSRIs are also prescribed to treat the symptoms of anxiety disorders, panic disorders, and other conditions that have been found to improve with increased levels of serotonin in the brain, such as Obsessive Compulsive Disorder (OCD). Mahmood et al. recorded only the depressive status of the participants, potentially neglecting the roles of these comorbid/related disorders in their results. Another important feature of the study is the selection of quotations to represent each of the themes. This inherently introduces bias to readers’ understanding of the themes and the participants, exemplified above in the discussion of Theme 1. The full interview transcription could not be incorporated into the article, so important nuances to the responses that were included may have been neglected. Indeed, some of the 20 participants were not quoted in the study at all. This is especially limiting because the sample is small and may not be statistically significant.
Additionally, the authors acknowledge that the representativeness of the study could be limited by the participant pool demographics, which are notably skewed white and female. This bias is pertinent to this study’s themes within the issue of antidepressant medication management because race and gender can profoundly affect depression care. The adequacy of care is compromised by racial and gender-based disparities (Hahm et al., 2015). Preferences for modes of treatment are influenced by cultural standards (Sonik et al., 2020), impacting an individual’s decision to take and/or stay on SSRIs. Even more specific to this study, discrimination in healthcare systems in the UK leads to poorer mental health treatment outcomes for women and marginalized ethnic groups. These phenomena highlight the lack, yet importance, of socially competent care.
Further studies on the subject of antidepressant withdrawal are necessary, and they should be more extensive and diverse so that conclusions can be more applicable to a larger group of people who take SSRIs. The implication of this study is increased awareness of the need for the role of GPs in antidepressant withdrawal to be further explored and more supportive. However, in psychiatric medication management, psychiatrists or psychiatric nurse practitioners who are trained in this role likely fulfill it better than most GPs. For this reason, future studies should explore their accessibility, impact, and—as previously highlighted—their ability to provide equitable care to the most marginalized.
Dana Ayebare is a staff writer at The Princeton Medical Review. She can be reached at da0539@princeton.edu.
References
Anekwe, C. (2022, July 18). Managing weight gain from psychiatric medications. Harvard Health. https://www.health.harvard.edu/blog/managing-weight-gain-from-psychiatric-medications-202207182781
Bamalan, O. A., Moore, M. J., & Al Khalili, Y. (2024). Physiology, Serotonin. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK545168/
Chua, K.-P., Volerman, A., Zhang, J., Hua, J., & Conti, R. M. (2024). Antidepressant Dispensing to US Adolescents and Young Adults: 2016–2022. Pediatrics, 153(3), e2023064245. https://doi.org/10.1542/peds.2023-064245
Gabriel, M., & Sharma, V. (2017). Antidepressant discontinuation syndrome. CMAJ : Canadian Medical Association Journal, 189(21), E747. https://doi.org/10.1503/cmaj.160991
Hahm, H. C., Cook, B. L., Ault-Brutus, A., & Alegría, M. (2015). Intersection of race-ethnicity and gender in depression care: Screening, access, and minimally adequate treatment. Psychiatric Services (Washington, D.C.), 66(3), 258–264. https://doi.org/10.1176/appi.ps.201400116
Marasine, N. R., Sankhi, S., Lamichhane, R., Marasini, N. R., & Dangi, N. B. (2021). Use of Antidepressants among Patients Diagnosed with Depression: A Scoping Review. BioMed Research International, 2021, 6699028. https://doi.org/10.1155/2021/6699028
Patient Health Questionnaire (PHQ-9 & PHQ-2). (n.d.). American Psychological Association. Retrieved May 2, 2024, from https://www.apa.org/pi/about/publications/caregivers/practice-settings/assessment/tools/patient-health
Sampaio, F., Gonçalves, P., & Sequeira, C. (2022). Mental Health Literacy: It Is Now Time to Put Knowledge into Practice. International Journal of Environmental Research and Public Health, 19(12), 7030. https://doi.org/10.3390/ijerph19127030
Sonik, R. A., Creedon, T. B., Progovac, A. M., Carson, N., Delman, J., Delman, D., Lê Cook, B., Soffer, T. F., Chambers, V., Quinerly, C. R., Mann, Z., Nabisere, R., Shaikh, F. N., Jordan, D., Moradi, A., de Castro, S., Abolaban, H., Lee, E., Shu-Yeu Hou, S., … Kaushal, N. A. (2020). Depression treatment preferences by race/ethnicity and gender and associations between past healthcare discrimination experiences and present preferences in a nationally representative sample. Social Science & Medicine, 253, 112939. https://doi.org/10.1016/j.socscimed.2020.112939
Thomas, T. (2023, December 5). Experts call for fewer antidepressants to be prescribed in UK. The Guardian. https://www.theguardian.com/society/2023/dec/05/experts-call-for-fewer-antidepressants-to-be-prescribed-in-uk
Wang, Y.-Q., Lin, W.-W., Wu, N., Wang, S.-Y., Chen, M.-Z., Lin, Z.-H., Xie, X.-Q., & Feng, Z.-W. (2019). Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis. Acta Pharmacologica Sinica, 40(9), 1138–1156. https://doi.org/10.1038/s41401-019-0217-9
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