An Evaluation of Anti-Depressants Versus Non-Medication Therapies on the Treatment of Depressive Disorders


By Divya Manikandan

Ever since the late 1900’s and straight into the 21st century, we have witnessed an increased marketing and usage of anti-depressants by the general population , with SSRI’s (selective serotonin reuptake inhibitors) such a Prozac, becoming household names. However, while these drugs may have their positives, their negative patho-physiological side effects remain largely undermined. This article aims to create an in depth analysis of the biological impact of various Anti-Depressant drugs in the treatment of depression, while also examining a range of non-medication related therapies, such as various forms of occupational therapies and evaluating their efficacy as anti-depressants.



The American Psychological Association defines Depression as more than a state of sadness.
Depression is a serious biological problem that results in numerous changes to the brain that results in the apparent change of behaviour that is associated with the illness.
A Meta-analysis published in the Journal of Affective disorder [1] identified, using brain imaging technology that the very structure of the brain changes during depression, in that the grey matter decreases in key regions of the brain such as the amygdala, limbic and prefrontal cortex.

Another study [2] explains that Depression is characterised by the decreased activity of the serotonergic systems of the brain which results in low levels of serotonin hormone. There was an additional note of irregularities in norepinephrine and dopamine levels in the brain, which was accompanied by the dysfunctional connections between the structures of the limbic system, cortical and hippocampal regions.

Further research studies [3] have also found that a lot of depressive symptoms are in fact associated with changes in the neural plasticity in the brain (which is the ability of neurons to form new circuitry and enhance the growth of that brain when information is learned)
If this neurogenesis and connection is promoted, the neurodegenerative tendencies of brain traumas, some of which are characteristic of depression, could be effectively reversed.

Of these three main physiological changes that occur in the brain during depression, a large emphasis has been placed on the levels of neurochemical mediators in the development of treatments.
It was long believed that a reduction in neurotransmitters such as dopamine and serotonin in the neural synapses as a result of increased reuptake, by vesicles into neurons ,was the regulating factors of depression. Drugs contained SSRI’s, which inhibit the reuptake of serotonin, were primarily developed to target this problem.

However with more extensive research on the topic, the efficacy of SSRI’s or any such neurotransmitter based antidepressant drugs has been called into question.
A meta-analysis conducted by Jay Fournier and his team at the University of Pennsylvania demonstrated that the efficacy of anti-depressants correlated strongly with the severity of depressive disorder of the individual.
This severity was quantified on the Hamilton depression scale wherein participants who had a depression rating of less than 25 on the scale rendered the drug to be of no clinical importance.[4]

Putting these findings into a global perspective, the CDC recorded in the year 2011, about 8% of US residents aged 12 and older were taking anti-depressants without even showing signs of major depressive disorder.
Additionally, they deduced that 14% of users had used the drugs for over a decade, and 33.33% of them had not seen a mental health professional in over a year. [5]
What these results point towards is the non-judicious use or rather misuse of antidepressants in the market which makes it crucial that an in-depth analysis of its pros, cons and alternatives is carried out.


As demonstrated in Fournier’s study, the use of Anti-Depressants in patients with severe depression is justified; however it is not only unnecessary but also harmful when taken in excess quantities, particularly by those who don’t need them. The most infamous side effects of these drugs are sexual dysfunction, insomnia, nausea and headaches.
Furthermore, a study conducted by Joseph Glenmullen[7] stated that along with inhibiting Serotonin reuptake in the neural pathways of the brain, SSRI’s can also pump quantities of this hormone into the brain, which can lead to damage to intricate brain structures.

Although this is not widely accepted in the scientific community, it is generally agreed upon that Serotonin does have the ability to have a negative impact on delicate nerve fibres.[6]
Further studies by researchers have also noted cases of Tachyphylaxis (which is the recurrence or worsening of a disease despite continuous treatment with a drug) when it comes to patients having Major Depressive Disorder taking Anti-depressants.

A study conducted by Solomon Et al. of The Department of Psychology at Brown University, followed 103 patients who were diagnosed with Major Depressive Disorder, for a span of two decades without intervening in their medication or treatment. Between these 103 individuals, there were 171 medical treatment interventions and it was noted that in of all these intervals, Tachyphylaxis occurred in 1/4th of the patients. [8]

[9]Dr. ElMallakh of the University of Louisville, states that in some cases consistent use of antidepressants can result Tardive Dysphoria, which is essentially when the antidepressants counterproductively induce depression in the patients.

In a literature review, El-Mallakh found that patients who ultimately presented with treatment resistant depression did initially demonstrate positive results when prescribed anti-depressants, and the researcher hypothesizes that this was a result of damage to brain plasticity that was instigated by the Anti-Depressants themselves.
[10]Another noteworthy finding published by Paul Andrews in the Frontiers in Psychology mentioned that the main purpose of anti-depressants is to reinstate hormonal homeostasis in the brain, however when the brain is deprived of the intervention there can be drastic and sudden surges in these levels of hormones which often leads to relapse of the disease anyway.

These effects are more commonly associated with the well versed physical dilemmas and difficulties of withdrawal, which is another unique disadvantage of Anti-depressant use, especially when the usage begins in formative teenage years.

Based on these studies and many more, it is evident that Anti- depressants are extremely useful in encouraging neurogenesis and neural plasticity, and vital in the maintenance of hormone levels in the brain and that they are a key miracle worker in life improvement of many individuals. However it is important to realise that anti-depressants are not necessarily a permanent solution in that not only do they have undesirable side effects, but are also unable to prevent relapse and treat chronic depression.

At this juncture in psychological history, it is crucial that we move away from the conventional methods of treating disorders and look for answers in non-medicated therapies, that may not only be more efficacious, but also more sustainable and less harsh on the body.



It has been long accepted that exercise is an essential key to physical and mental being, but recently scientists are beginning to understand how exercise can prove to be a therapeutic tool as well.
[11]A review conducted by George Mamma, and Guy Falkner examined around 30 studies that aimed to relate exercise and mental health, out of which 25 of the studies demonstrated a negative correlation between exercise and the number of times an individual had a recurrent bout of the illness.
[12]Similar results were also found in a study conducted by Alex H.S Harris at the Centre for Health care evaluation, which demonstrated that physical activity was associated with a lower rate of subsequent depression.

[13]Regular levels of physical activity have been positively correlated to the increase of BDNF (brain derived neurotrophic factor) which is responsible for increasing the neuroplasticity of the brain. It is also instrumental in rehabilitating basic circadian rhythms, appetite, desire for activity and such mechanisms that usually disrupted by depression, by enhancing the hypothalamus’s functioning.
[14]A literature review by Arthur F. Kramer, Kirk I. Erickson, Stanley J. Colcombe in the Journal of Applied Psychology also found that the exercise in rats halted dopamine reduction levels and stimulated an increase in serotonin and acetylcholine levels, associated with pleasure, regulation and memory respectively.

[15]When evaluating the efficacy of medicated versus non medicated therapies in terms of
exercise, it is important to consider studies that compare the two.
A study conducted by Lynnette Craft and Frank Perna from the Boston school of Medicine compared individuals with depression by placing them into three groups: Exercise, Medication and Both combined.

Over the four month trial period it was noted that although the medicated group noted a faster amelioration of symptoms, at the end of the trial all the groups had the same depression scale value which demonstrates that on a short term level, exercise is as efficacious as an antidepressant.
After another 10 months when a follow up study was conducted however, it was noted that when participants had performed the exercise over a longer period, they had higher relief rates as compared to both the medicated and the combined group, which calls into question the idea whether the use of anti-depressants can not only be less efficacious but also redundant as opposed to exercise (taking into account that the depression type varies only from mild to moderate).


Meditation can essentially be described as a process that propels an individual to focus purely in a stress free zone, ultimately leading to a calmer and more collected mind frame.
While the notion that meditation is a healthy practice has been around for a long time, its employment as a treatment for depression is rather revolutionary and even has a therapy form built around it: Mindfulness cognitive therapy.
The foundation of meditation is to clear the pathways of thinking and helping individuals shift their focus and look at stressors and events in new and positive perspectives.

[16]A study conducted by a Britta K Holzel of MassGen medical centre and her team examined participants who were in need of stress reduction at the University of Massachusetts Medical centre. The participants were subjected to around 8 weekly doses of mindfulness cognitive therapy (meditation sensations) at the end of which they had to undergo MRI scans that revealed a portion of increased grey matter concentration in the hippocampal regions of the brain. These same results were further recognised in the cerebellum and posterior cingulate cortex as well.
The increase in grey matter in such vital regions of the brain suggests that it could be linked to an overall increase in mental health and functioning.

[17]A paper by A. B. Newberg and J. Iversen of UPenn and Stanford University respectively, aptly describes the entire neurotransmitter circuitry that occurs during meditation.
Their paper demonstrates that meditation not only activates the aforementioned brain regions but also activates a part of the autonomous nervous system that can stimulate various parts of the hypothalamus that can release serotonin (whose deficiency is a major biomarker of depression).
This surge of serotonin not only boosts positive mood levels but further triggers a dopaminergic response which activates the pleasure centres of the brain. These two neurotransmitters then work together to activate acetylcholine and melatonin in the brain.
This influx of neurotransmitter activity ultimately helps in the regulation of sleep cycles, appetite and overall mood which can alleviate the major symptoms of depression.

Cognitive Behaviour Therapy

[18]CBT is a subpart of psychotherapy which is a goal oriented model of the therapeutic methods used to primarily deal with illnesses such depression.
The therapy was developed in the 60s by Aaron Beck. CBT involves building an ideal and healthier model for the patient to look towards as the goal. Over the course of the treatment the individual is conditioned to be motivated by that model which ultimately helps alleviate the negative symptoms. The therapy many focuses on what negative thoughts the patient may be harbouring and trying to understand why those thoughts began to start- while carrying out a thorough analysis of emotional thinking patterns and childhood family histories.

[19]A study conducted by Rush et al in “Cognitive Therapy and Research” examined the effect of CBT on 41 participants that were randomly assigned to CT for an average of 10.9 weeks or to a dosage of Imipramine (a tricyclic antidepressant) for around the same time.
Around 3/4ths of the group had suicidal thoughts with a mean depression duration of “8.8” years.
The final results were measured on standardised scales such as the Beck inventory and the Hamilton Depression scale and it was found that although both the groups showed reduction in depression levels, however around 79% of the CBT group showed remission signs as opposed to 22.7% of the Imipramine group.
[20]Similar results have been found by another study conducted by Anthony Spirito that controlled for multiple other SSRI’s and antidepressants such as Flouxetine in adolescents with suicidal tendencies.


Based on all this amalgamated data from so many scientists and researchers cited, one thing is clear: To large extent non medicated therapies can as beneficial, perhaps even more successful, in preventing relapse into some cases of depression than medicated therapies can.
This is not to say that medication has not been efficacious in bettering the lives and mental health of millions of individuals around the globe; however it has been known to cause addictive symptoms and unhealthy side effects.
This situation can be avoided with sustainable and equally helpful measures as the listed therapies above, which also contribute to relaxation in the cases of meditation and exercise or overall personality development in the case of psychiatric therapy.

It is plausible that at least in the near future, a psychiatrically approved involvement of both therapies could be useful to provide immediate relief as well as long term treatment for mental illness such as Depression.



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3) Jacobs, B. L., Praag, H. V., & Gage, F. H. (2000). Adult brain neurogenesis and psychiatry: a novel theory of depression. Molecular Psychiatry, 5(3), 262-269. doi:10.1038/

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5) Antidepressant Use in Persons Aged 12 and Over: United States, 2005–2008 Laura A. Pratt, Ph.D.; Debra J. Brody, M.P.H.; and Qiuping Gu, M.D., Ph.D.

6) Do Antidepressants Permanently Rewire the Human Brain? (n.d.). Retrieved February 19, 2017, from

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8) Solomon, D. A., Leon, A. C., Mueller, T. I., Coryell, W., Teres, J. J., Posternak, M. A., . . . Keller, M. B. (2005). Tachyphylaxis in Unipolar Major Depressive Disorder. The Journal of Clinical Psychiatry,66(03), 283-290. doi:10.4088/jcp.v66n0302

9) El-Mallakh, R. S., Gao, Y., Briscoe, B. T., & Roberts, R. J. (2011). Antidepressant-Induced Tardive Dysphoria. Psychotherapy and Psychosomatics,80(1), 57-59. doi:10.1159/000316799    

10) Andrews, P. W., Kornstein, S. G., Halberstadt, L. J., Gardner, C. O., & Neale, M. C. (2011). Blue Again: Perturbational Effects of Antidepressants Suggest Monoaminergic Homeostasis in Major Depression. Frontiers in Psychology,2. doi:10.3389/fpsyg.2011.00159

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15) Craft, L. L., & Perna, F. M. (2004). The Benefits of Exercise for the Clinically Depressed. The Primary Care Companion to The Journal of Clinical Psychiatry,06(03), 104-111. doi:10.4088/pcc.v06n0301

17) Newberg, A., & Iversen, J. (2003). The neural basis of the complex mental task of meditation: neurotransmitter and neurochemical considerations. Medical Hypotheses,61(2), 282-291. doi:10.1016/s0306-9877(03)00175-0

18) Beck, J. S. (2010, January 30). Cognitive Therapy. Retrieved June 12, 2017, from

19) Rush, A. J., Beck, A. T., Kovacs, M., & Hollon, S. (1977). Comparative efficacy of cognitive therapy and pharmacotherapy in the treatment of depressed outpatients. Cognitive Therapy and Research, 1(1), 17-37. doi:10.1007/bf01173502

20)Spirito, A., Esposito-Smythers, C., Wolff, J., & Uhl, K. (2011). Cognitive-Behavioral Therapy for Adolescent Depression and Suicidality. Child and Adolescent Psychiatric Clinics of North America, 20(2), 191-204. doi:10.1016/j.chc.2011.01.012



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