Volume 2 Issues 8 August, 2021
Consultation Liaison Psychiatry Focus: Pharmacology
An Overview
In search of better tolerability for treatment of Depression, which is a disorder of mood, SSRIs were first introduced in 1987-88. Some of commonly used SSRIs are- Fluoxetine, Fluvoxamine, Sertraline, Paroxetine, Citalopram, Escitalopram. Currently these are the most commonly prescribed antidepressant drugs.
Understanding Mechanism of action: – Brain works through numerous transmitters like Norepinephrine which acts as neurotransmitter at Hypothalamus (eating, drinking, sexual behavior, sleep, circadian rhythm), Limbic system (emotional status), RAS (wakefulness) , 5HT acts as neurotransmitter at Cerebral cortex ( judgment, memory etc.,) hippocampal areas (learning, emotional status) & raphe nucleus. Depression, which is thought to be of varied etiology, leads to functional deficit of number of neurotransmitters, predominantly Norepinephrine and/or 5-HT in CNS. SSRIs exert their therapeutic effects through 5-HT reuptake inhibition. They selectively increase the levels of serotonin in the synaptic cleft by blocking reuptake by 5HT neurons. Patients have to be educated that 2-3 weeks is required to produce desirable effect.
Advantages :- Unlike TCAs (Tricyclic antidepressants) the SSRIs have less sedation, less interference with cognitive & psychomotor functions, least anticholinergic actions, No postural hypotension (α), No seizure precipitation, No effect on cardiac conduction, less nausea (tolerance develop over a period of time).
Therapeutic uses: In Depression- goal is to resolve symptoms, to prevent relapse & prevent recurrences. In general SSRIs are better in comparison to TCAs (tolerability and safety in overdose) especially in patients with suicidal ideations.
If a drug has to be changed- up titration of new drug & down titration of earlier drug is practiced. While stopping the dose should be tapered over a period of at least 6 weeks to avoid discontinuation symptoms (anxiety, agitation, nausea) They are also used in treatment of Panic disorders, Obessive Compulsive disorder (OCD) :- Social phobia, Post Traumatic stress disorder, Eating disorder, Premenstrul disorder, Compulsive buying and impulse control disorders.. Like gambling and kleptomania (uncontrollable desire to steal things of less significance) Naturally available serotonin in some fruits is thought to be beneficial for feel good factor even in non depressed patients.
Important side effects are:-
1. On initiation: Gastritis, GI bleed, loose stools, agitation, anxiety and insomnia.(dose titrated upward more slowly), Sexual dysfunction ( decreased libido , delayed ejaculation and anorgasmia ). The delayed ejaculation has been utilized for treatment of patients with premature ejaculation!!! Higher doses provide weight loss, Paroxetine can cause – weight gain.
2. Sudden withdrawal (paroxetine and sertraline) leads “discontinuation syndrome”- dizziness, paresthesias and head ache.
Drug interaction
1. Elevate plasma levels and toxicity of TCAs, haloperidol, clozapine, warfarin, dextromethorphan ( retarding metabolism)
2. with MAOIs- elevated levels of 5-HT in synaptic cleft leading to “Serotonin syndrome” ( hyperthermia, muscle rigidity, tremors, rapid changes in mental status and cardiovascular collapse- reduced metabolism, inhibited uptake and pronounced release of 5 HT )
SSRIs may have seen more acceptances based on tolerability & safety profile but Tricyclic Antidepressants are still considered gold standard against which all antidepressants have to be compared in terms of efficacy.
JSS Medical College, Mysore
