Class of Antidepressant

Selective serotonin reuptake inhibitor (SSRI) is the class of antidepressant medication chosen

for the focused research. SSRIs are classified as the newer drugs that have been developed to

treat depression. They have fewer side effects, are safer, effective, and thus are more

acceptable (O’Neal et al., 2021). Selective serotonin reuptake inhibitors (SSRIs) are the most

commonly prescribed class of antidepressant. For major depressive disorder, which affects as

high as 20% of adults, SSRI’s are considered as one of the front-line treatments(Jha et al ,

2018). While it said these drugs have fewer side effects it is reported that some people who

take them for several months can develop a syndrome that mimics the depression that this

drug is supposed to be treating. The symptoms of this syndrome include energy loss,

passivity, cognitive flattening, apathy, anhedonia and decreased sex (O’Neal et al., 2021).

The different types of SSRIs are fluoxetine (Prozac) the first one that was developed,

citalopram (Celexa), escitalopram (lexapro), fluvoxamine (luvor), paroxetine, (paxaland and

sertraline (zoloft).

Mechanism of Action of SSRI’s

As the abbreviation implies SSRI’s selectively inhibit the reuptake of serotonin at serotonin

receptors. Consequently, there is a concomitant increase in the serotonin concentrations in the

synaptic cleft leading to stimulation of the post synaptic serotonin receptors.[Perez-Caballero

et al(2019), Knorr et al (2019) and Hillhouse et al (2015). Joshi (2018) further elaborated that

the therapeutic effect of SSRI’s is caused by regional blockade of presynaptic serotonin

transporter (SERT). The dorsal raphe-originating neurons(DRN) as well as the hippocampi,

amygdala and prefrontal regions have large quantities of SERT. The aforementioned
structures are thought to be responsible for the manifestations of the depressive condition.

According to Joshi (2015) the blockade causes an increase in the extracellular concentration

of 5 HT. This facilitates the opening of G-Protein coupled potassium channels via the

activation of inhibitory auto-regulators. The end result is neuronal hyperpolarization and an

attenuation of 5-HT transmission. Joshi (2015) further purports that there are two types of 5-

HT receptors that mediate G-coupled neurotransmission. These are 5-HT1A and 5-HT1B .

They are associated with adenyly cyclase inhibition and a dampening in serotonergic

transmission.

Potential Home Remedies and Natural Supplements

According to Oladi (2021) several herbal medicines have shown potential in treating

depression based on the concentrations of vitamins and other constituents that thay contain

These include : Seaweed and Blue Potatoes ( large quantities of iodine), red peppers (high

vitamin C levels), coconut (medium chain triglycerides are thought to be neuroprotective),

pumpkin seeds and asparagus ( high levels of tryptophan), mussels (high vitamin B12 levels),

Swiss Chard (high magnesium) and cherry tomatoes (great source of lycopene)

Some herbal medicines have actually been approved for treating depression based on

recognized efficacy, clinical publications and acceptable levels of safety. According to

Fajemiroye et al (2016) Piper Methysticum(Kava) derived products by National Agency of

Sanitary Surveillance (ANVISA) in Brazil as well as Hypericum Perforatum (St. Johns Wort)

by European Medical Agency (EMA) are among the list of Herbal Medicines for the

treatment of depression.

Hypericum Perforatum contains hypericin and hypertocin. Fajemiroye et al cited

research by Klemow et al (2013) and Kaehler et al (2003) that states that the hypericin
compound has a strong affinity for sigma receptors through which it regulates dopamine

levels thus accounting for its antidepressant activity. In addition, the hypertocin component

enhances extracellular levels of several neurotransmitters including serotonin, dopamine,

GABA, Noradrenergic and L-Glutamate.

Fajemiroye et al cite work by Schirmacher et al (1999) supporting the use of Piper

Methysticum (KAVA) in the treatment of depression. The mechanism of action of KAVA is

via inhibition of MAO-B and blockade of the uptake of noradrenaline according to

Fajemiroye et al as cited in the work of Uebelhack et al. Oladi (2021) concurs that St. John’s

Wort and KAVA may be used to treat depression.

Possible Drug/ Supplement interaction

Woron et al (2018) in their analysis of the antidepressant group concluded that

adverse drug interactions with herbal remedies were confined mostly to serotonin or

serotonin and noradrenaline reuptake inhibitors. The herbal products most likely to cause

significant pharmokinetic and pharmacodynamic interactions were especially those

containing ginseng, rhodiola rosea, ginkgo biloba or milk thistle extract. Haemorrhagic

complications were the most commonly encountered effect of these herbal supplements when

used in conjunction with SSRI’s mainly due to the combination with Japanese ginkgo biloba.

The serotonin syndrome was a common manifestation (11.8% of complications), most

commonly occurring during the use of Japanese ginkgo biloba (27.45% of complications),

ginseng (25.5%); rhodiola rosea (15.7%) and milk thistle (11.8%).

As a clinician it is of paramount importance to use current resources. New data from

in vitro and human herb-drug interaction studies are being published regularly. Examples of

reliable sources include PubMed, Natural Medicines database, the Allied and Complementary
Medicine Database, Lexi-Natural Products, and the National Institutes of Health's Office of

Dietary Supplements(Asher et al). For example ,St. Johns Wort has received approval by

European Medical Agency (EMA) as a Herbal Medicine for the treatment of depression.

However drug interactions with St. John's wort are highly likely. As a consequence,

concurrent use with prescription medications(especially SSRI’s) are avoided.

The interaction risks primarily based on human studies of major cytochrome P450 enzymes (i.e., 1A2,

2C9, 2C19, 2D6, 2E1, and 3A4) and P-glycoprotein.

Client using supplemental treatments to address their depression

According to Asher et al (2017) supplement use in conjunction with prescription

medication occurs in 25% of Americans. To further compound matters most patients are

reluctant to disclose supplement use to clinicians. The degree of clinically important drug

interactions varies. In order to anticipate and detect herb-drug interactions it is important to

develop a trusting clinician-client relationship that encourages the discussion of dietary

supplement use. As clinicians we should collaborate and consult dietary supplement

resources that are reliable and valid based on evidence based criteria. Communication with

clinical pharmacists or pharmacologists, can also help assess specific herbal supplement–drug

combinations for safety.

In addition, product quality is important. Asher et al cites numerous reports of

contaminants such as pesticides, heavy metals, and bacteria. In addition the issue of

adulteration with prescription medications or other plant material, continue to surface. It is

also difficult to determine that a supplement contains adequate concentrations of active

components.
 Woron et al (2018) advocates that any decision to use a herbal supplement must take

into consideration the resulting complications and side effects. The fact that undesirable

interactions may occur would be discussed with the patients with respect to the nature

(bleeding, dystonia, excessive sedation, pancreatitis, serotonin syndrome, etc.), as well as the

proposed course of action to undertake in the event of adverse symptoms. Any inclusion

would be preceded by a detailed safety analysis as well as benefit and risk assessment. Asher

et al (2017) clearly states that with regards to patients taking SSRI’s , if there is a paucity of

data or no data are available on the potential for specific herb-drug interactions one should

adopt a conservative approach and not to recommend supplement use.

It should be noted that these interactions are infrequent therefore herbal supplements

may be used concurrently with the proviso that patient monitoring for adverse effects may be

is practiced , its clinical effects are readily monitored, and predetermined drug concentrations

are not being targeted. Consultation with a clinical pharmacist or pharmacologist may be

helpful when evidence is unclear as cited by Asher et al (2017). This will help to determine

whether there is a pharmacokinetic/ADME interactions or pharmacodynamic interactions.

This will aid informed decision making about whether to adjust the drug's dosage or

discontinue the supplement.

Safer alternatives