Background

            Mental illness is
a condition that affects a person’s ability to work, sleep and socialize. It is
often accompanied with a feeling of sadness, self-worthlessness and lack of
motivation. According to the American Psychiatric Association “19% one in
five of adults in the United States experience some kind of mental illness”. Mental
illness, like depression and chronic stress, stems from several factors such as
abnormal levels of neurotransmitters in the brain, which is the main focus of
this research. Treatment of mental illness has focused primarily on the
monoamine hypothesis which states that the decreased level of serotonin,
norepinephrine and dopamine concentration in the brain is the essential reason
behind brain pathophysiology (Bunney and Davies, 1965)1,6.

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Serotonin, norepinephrine and dopamine are neurotransmitters that are involved
in modulating multiple functions including emotional process, mood, sleep and
hormone secretion. The monoamine hypothesis of depression has been proposed
almost 50 years ago. Currently, the most popular and prescribed antidepressants
such as Prozac, which was approved by FDA in 1987, follow the monoamine
principle in treating depression. This particular kind of drugs are classified
as selective serotonin reuptake inhibitors (SSRIs). SSRIs work by selectively
inhibiting and preventing serotonin from being reabsorbed at serotonin receptor
sites. As a result, this inhibition increases serotonin concentration at the
synaptic cleft; thus, stimulating the postsynaptic serotonin receptors more. SSRIs
are just one class of antidepressants that depend on the monoamine hypothesis,
other classes include monoamine oxidase inhibitors and tricyclic
antidepressants. However, SSRIs are the most common since they are considerably
safer and relatively cause fewer side effects. Nevertheless, there are some
limitation to the current antidepressants and their effectiveness. According to
information published at the U.S National Library of Medicine and updated in
2017, questioning the success of antidepressants in effectively preventing
relapses:

Antidepressants
are usually taken for one to two years, sometimes longer, to prevent relapses.

Studies involving adults on commonly used antidepressants such as SSRIs lower
the risk of relapse but it cannot completely prevent them. Also, studies show
that 50 out of 100 people who took placebo had a relapse within one to two
years. And 23 out of 100 people on antidepressants had a relapse within the
same period. This means taking antidepressant for longer period prevent relapse
in 27 out of 100 people on average.2,8,13.

 

In addition to the high rate of relapses, antidepressants are typically
accompanied with side effects such as mouth dryness, anxiety, headaches, and
low sex-drive. Moreover, data from several observational papers states that the
use of SSRIs may reduce the probability of suicide in adults. However, among
teenagers the use of SSRIs may increase the risk of suicide (Barbui, Esposito
& Cipriani, 2009)3,7,17. Furthermore, there have been small
number of reports of severe side effects like problems related to the heart,
liver and kidney of patients on antidepressants (2).

Uncertainty surrounding antidepressants and their effectiveness
have led research to shift its focus from the monoamine hypothesis to the
glutamate system as the key player behind brain pathophysiology. Therefore,
offering new therapeutic drugs that has the potential in curing mental illness
in less time and fewer side effects. However, the shift is slow and there is
still currently no FDA approved antidepressant that rely on glutamate.