An overview of atypical anti depressants

This powerpoint presentation deals with the pharmacology and psychiatric uses of atypical anti-depressants. TCAs and SSRIs are considered as typical anti-depressants, while other classes include SNRI, RIMAs and atypical antidepressants. In this presentation, i have briefly given an overview of atypical anti-depressants as well as of SNRIs and RIMAs.

1. Atypical Anti-depressants Brajesh Lahri Final Professional MBBS Student All India Institute of Medical Sciences (AIIMS), Bhopal

2. By the end of discussion you should be able to… Classify anti-depressants Enlist atypical anti-depressants Know about the mechanism of action of atypical anti-depressants Know about the indications of atypical anti-depressants Know about the side effects of atypical anti-depressants

3. Introduction Major Depression and Mania are two extremes of affective disorders, referring to pathological change in mood state. Depression is characterized by symptoms like sad mood, loss of interest and pleasure in activities, low energy, feeling of guilt, agitation, change in appetite, sleep disturbances, suicidal thoughts etc. Anti-Depressants are drugs which help to elevate mood in depressive illness.

4. Pathophysiology of depression Many theories are given, most accepted is Monoamine Hypothesis. It states that deficiencies in various monoamine neurotransmitters are responsible for corresponding symptoms of depression . According to the monoamine hypothesis, Serotonin , norepinephrine, and dopamine are the neuro-transmitters associated in pathophysiology of depression . ** ( Serotonin, Nor-epinephrine and Dopamine levels are decreased in depression)

5. Classification of Anti-Depressants

6. Atypical Anti-depressants Mirtazapine Trazodone Bupropion Tianeptine Agomelatine

7. Mirtazapine Mechanism of Action Blocks α -1 receptors (present on NA neurons) and Hetero receptors (5HT-2) (present on 5-HT neurons), enhancing both NA and 5HT release. ** Also, Mirtazapine is said to have some affinity for α -2 receptors, which is claimed to be related to their therapeutic efficacy, but this point is questionable. **(It is also a H1 blocker and quite sedative) Adverse Effects Increased appetite Weight gain Agranulocytosis (Rare) Indications : Depression, OCD, Panic disorder, PTSD, SAD

8. Trazodone Mechanism of Action Prominent α -1 adrenergic and weak 5-HT 2A antagonistic action . Also acts by blocking uptake of 5HT . Adverse Effects - Excessive Sedation - Inappropriate, prolonged and painful penile erection (Priapism) Postural Hypotension (Due to α 1 adrenergic blockade) Indications : Generalized anxiety disorders (GAD), Panic Disorder, Eating Disorders

9. Bupropion Mechanism of Action Inhibits re-uptake of Dopamine and Nor-Adrenaline. In addition may also increase the release of NA and DA. **(It has excitant rather than sedative activity) Adverse Effects - Insomnia and agitation Decreases Seizure threshold Indications : Depression, Eating Disorder, Cannabis dependence, Cocaine dependence, Nicotine dependence

10. Agomelatine Mechanism of action: It acts as melatonin receptor agonist at MT1 and MT2 receptors. It also acts as a weak antagonist at 5-HT2c receptors Adverse Effects : - Nausea and Dizziness - Increase in liver enzyme levels Indications : Depression, resynchronization of disturbed circadian rhythm

11. Tianeptine Mechanism of Action : It increases serotonin/5-HT uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites . Adverse Effects: Nausea, Constipation, Abdominal Pain Dizziness, Headache Hepatoxicity (Rare ) Indications : Useful in anxio -depressive states ,as well as in endogenous depression

12. Serotonin and Nor-Adrenaline reuptake inhibitors (SNRIs) Venlafaxine Duloxetine Mechanism of Action : Inhibit uptake of both Nor-adrenaline and Serotonin , but do not interact with cholinergic, adrenergic or histaminergic receptors. Adverse Effects : Dizziness ,Insomnia Rise in BP (More common with Venlafaxine ) Associated with increased risk of Cardiac arrhythmias (Clinical significance is still unclear) Indications: - Depression (Both) - Neuropathic pain (Duloxetine)

13. Reversible Inhibitors of MAO-A (RIMAs) Moclobemide Clorgyline Mechanism of Action: Inhibit MAO-A enzyme which deaminates 5-HT and NA. Adverse Effects : -Nausea - Dizziness, Insomnia - Liver damage (Rare) Indications: Depression and Social Phobia

14. References Clinical Pharmacology-11 th Edition - Bennett, Brown and Sharma Goodman-Gilman’s -The Pharmacologic basis of Therapeutics- 12 th Edition – Brunton , Chabner , Knollmann Essential Medical Pharmacology-7 th Edition - K.D. Tripathi Essential Evidence based Psychopharmacology- 2 nd Edition- Stein , Lerer and Stahl

15. Thank You