Depression is a mental illness characterised by serious dysfunction, disability, and low quality

of life in those who experience them. It leads to depressed mood, negative thinking, lack of
enjoyment, reduced energy and slowness. They also place a heavy strain on those who
(41,42).
provide care for those affected The symptoms of depression are largely varied and its
presentation may vary. It may include psychomotor agitation or retardation to symptoms
mimicking dementia which in this case is just pseudo dementia.

Neurotransmitters like serotonin(5HT), noradrenaline and dopamine also called as

monoamine neurotransmitters are implicated in monoamine hypothesis of depression which
suggest an abnormality in a monoamine neurotransmitter system at one or more sites in the
brain. 41

Different class of antidepressants act on different neurotransmitters to treat symptoms of

depression. Some antipsychotics are also used as adjuvants to treat depressive symptoms
which may be difficult to treat with classical antidepressants alone. Amisulpride is one such
antipsychotic belonging to second generation of antipsychotics used in low doses along with
antidepressants.41 .

In the present study, the efficacy of combined treatment of Escitalopram plus Amisulpride
versus Escitalopram alone among patients with Depression was studied. Since antidepressant
and antipsychotics take around 4-6 weeks to improve the symptoms of depression, current
study was also done for 6 weeks with assessment at midpoint at 3 weeks.

In the present study, the subjects were divided into

two groups, i.e., group A and group B. Group A patients received only Escitalopram for the
treatment of Depression while Group B patients received Escitalopram and Amisulpride
(combination).

It was found that the mean age of participants in Group A was 34.60±7.85 years, and the
mean age of participants in Group B was 36.68±10.05 years. The mean age of onset of illness
among participants in Group A was 34.33±7.89 years, and in Group B, it was 36.13±10.06
years.
The reported mean duration of illness of participants in Group A was 1.67±0.72 months, and
the mean duration of illness of participants in Group B was 1.66±0.76 years. These results are
correlated with the study performed by Kaul V et al. (2015), who reported that the mean age
of the study participants was 46.84±1.10 years (43). Similarly, Dutta S et al. (2014) and
Grover S et al. (2013) also reported that the most commonly involved age group was 30-51
years 44,45 .

It was reported that there were changes in the HAM-D scale at various time periods in all the
patients. Statistical analysis showed that there was a statistically significant change from 0 to
6 weeks in depressed mood, feeling of guilt, suicide, early insomnia, middle insomnia, late
insomnia, work and activities, psychomotor retardation, agitation, psychological anxiety,
somatic anxiety, GIT somatic symptoms, somatic symptoms general, genital symptoms,
Hypochondriasis, weight loss and total HAM-D score. No statistically significant change was
observed in insight from 0 weeks to 6 weeks in both groups.

The study results showed that a combination of Escitalopram and Amisulpride was more
effective than monotherapy (Escitalopram). These results confirm that combination therapy is
superior than monotherapy in reducing symptom severity of depression in a small duration of
time; although both groups reported statistically significant symptom reduction.

Another similar study carried out by Kaul V et al. (2003) conducted a 15-week trial in which
Escitalopram and Amisulpride were compared for the treatment of depression patients over
HAM-A. The findings of the study suggest that Amisulpride and Escitalopram were both
helpful in lowering anxiety feelings in patients with Depression. Over the course of the
research, both groups' HAM-A showed a highly significant improvement. When baseline and
15 weeks were compared within the groups, both showed significantly substantial
improvement. When the study's fifteen weeks were up, an intergroup comparison was
conducted, and no discernible differences were found. It indicates that Escitalopram and
Amisulpride are equally efficacious in improving the HAM-A and reducing anxiety
symptoms in depression patients 43

In CGI-S , there was a statistically significant difference between group A and group B in
global improvement scores at 3 weeks and 6 weeks. The mean global improvement score at 3
weeks and 6 weeks in group B was significantly higher than that in group A. Also, there was
a statistically significant difference between group A and group B in efficacy index scores at
3 weeks. The mean efficacy index score at 3 weeks in group B was significantly higher than
that in group A.
The findings in our study suggest that combination therapy with Amisulpride
is better than monotherapy in reducing the symptom severity at 3 weeks and 6 weeks . These
findings are similar to the study conducted by Mansoor et al who conducted similar study of
amisulpride augmentation with antidepressants and reported significant improvement in
patients with treatment resistant depression. They also reported significant high rates of
response and remission in patients of depression although the study was limited by its small
duration size that is 6 weeks.

In the current study, no statistically significant change was shown in the ASEC scale at
various time periods in group A. Where as in group B, statistically significant changes were
found from 0 weeks to 6 weeks in nausea/vomiting, sexual dysfunction, and weight gain of
the ASEC scale. A statistically significant change was found in the GASS scale among group
B participants from 3 weeks to 6 weeks in prolactenemic S/E and weight gain for all the
patients.

These findings confirm the basic understanding that combination therapy leads to more side
effects than monotherapy but these side effects could be easily reduced or removed by
removing the antipsychotic in the later phases of treatment or by reducing the dose of the
amisulpride.

These results are consistent with the study conducted by Yongjun L et al. (2020), which
discovered that the combination of Escitalopram and Amisulpride is highly effective in
treating depression in patients over 65 years of age. It also has a higher safety profile. As the
study group had a higher overall effective rate of Depression than the control group,
following treatment, the study group and the control group's Symptom Checklist 90 (SCL-90)
scores were lower than before treatment, with the study group's scores being lower than the
control group's; the study group also experienced fewer side effects 46 .

In Investigations only mean systolic pressure, mean diastolic pressure and mean prolactin
levels were statistically significant. The mean systolic blood pressure at 6 weeks was
significantly higher in Group A than in Group B. The mean diastolic blood pressure at 6
weeks was significantly higher in Group A than in Group B. The mean prolactin level at 6
weeks was significantly higher in group B than in group A. Other differences were not
statistically significant. These findings suggest that combination therapy with amisulpride
leads to increased prolactin levels although no elevated Blood pressure levels were noted due
to lower doses of combination therapy used as compared to Group A.

Our results also corresponded with a multicenteric, randomized, double-blind, placebo-

controlled trial conducted by Bose A et al. (2008) in adult GAD sufferers, wherein
escitalopram and venlafaxine extended release were contrasted 47. Additionally, Escitalopram
proved to be highly successful when Soares CN et al. (2010) examined the safety and
efficacy of desvenlafaxine with Escitalopram in treating postmenopausal women with MDD
and anxiety symptoms 48 .

Given its established pharmacological profile, Amisulpride's distinct therapeutic profile has
been challenging to explain. It has been proposed that Amisulpride's therapeutic potential
may be explained by some evidence of limbic vs striatal selectivity and selectivity for
49
presynaptic dopamine autoreceptors, especially at low dosages . The blocking of
presynaptic D2 and D3 autoreceptors increases the dopamine concentration by decreasing the
negative feedback. This activity of amisulpride may be responsible for the antidepressant
property of the amisulpride as an augmenting agent with antidepressant (Mansoor et al
2015)

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) that is allosteric and may be
more effective than other SSRIs in treating severe depressive disorder. A meta-analysis
conducted by Ali MK et al. (2011) concluded that Escitalopram exhibits greater efficacy
when compared to both citalopram and the combination of SSRIs. Although there aren't as
many studies in these comparisons, Escitalopram and serotonin noradrenaline reuptake
inhibitors exhibit comparable efficacy. Though small, the differences in effectiveness are
clinically significant, particularly in patients with more severe depression 50.

Mandal T et al. (2021) determined whether the type of depressive episode, gender, and
baseline depression severity affect the safety and effectiveness of Escitalopram (10–20
mg/day) in patients with major depressive disorder (MDD) from South India. According to
the study, Escitalopram has a positive safety profile and is effective in treating MDD patients
from South India. While more ADRs were reported by male patients, the efficacy was
determined by the degree of the Patient's baseline depression. Of the 148 participants who
finished the 12-week trial, 42.6% and 43.9%, respectively, experienced remission and
response. At every follow-up appointment, there was a substantial decrease in the baseline
HDRS-17 and MADRS scores, and a similar pattern was observed with CGI. When
comparing the moderate baseline depression group to the severe depression group, the
efficacy outcomes were superior. Efficacy did not correlate with either gender or kind of
depressive episode. Over the course of the trial, 119 participants (80.41%) suffered at least
one adverse drug response (ADR) out of the 247 ADRs that were reported. There were no
reported major ADRs. Depending on the type of depressive episode and the degree of
baseline depression, escitalopram's safety profile was comparable in all groups 51.

Rittmannsberger H (2019) conducted the vast series and review of the literature regarding
amisulpride use as an augmentation agent for depression treatment resistance and concluded
that Amisulpride is a useful augmentation medication for the management of Depression.
This medication is unique in that it acts quickly and has a high degree of effectiveness.
Except for weight gain and elevated prolactin levels( which occur due to D2 blocking
property of amisulpride it also blocks dopamine transmission on the anterior pituitary’s
lactotroph cells, hence increase in prolactin), which happen even at the low dosages used to
treat Depression, side effects are insignificant.

The study concludes that amisulpride is an effective augmenting agent when used along with
Antidepressants , which leads to rapid recovery in depressive symptoms as amisulpride has
quick action in comparison to Antidepressants , the only thing which we need to take care
of ,is the side effects of amisulpride like weight gain and hyperprolactinemia.34