Everything you need to know about Depression pathology, non-pharmacologic and pharmacologic therapeutics, epidemiology and clinical pharmacology فارماکولوژی بالینی افسردگس (انگلیسی)

1. “ living with a
BLACK DOG … "
Clinical Pharmacology
Mohammad.J Rajabi

2.  What is Depression?
 Epidemiology, Economics
 Pathophysiology
o COVID-19 and depression
 Therapies
o Non-Pharmacologic
o Pharmacologic
 Case (86-1)

7. Epidemiology, Economics
• Eu and USA: 4.1% and 6.7%
• onset of depression 20s (first episode: any age)
• Women Vs Men
• Genetic
• Socioeconomic Conditions
• Stressful Events (i.e. environmental factors)
• 2015: 210.5 B$ (1$:1.9 $, 385.9 B $)

8. Pathophysiology

9. Neuroendocrine and Neuroimaging Findings
Abnormal thyroid function tests
Clinical hypothyroidism vs thyroid supplementation
HPA: CRF and CS (antidepressant and ECT)
Hypercortisolemia reducing gray matter
Corticosteroids and modulate serotonin synthesis
Increased inflammatory cytokines
Neuroimaging
limbic structures and prefrontal cortex, hippocampal loss

10. Testosterone
vs
Estrogen

11. Non-Pharmacologic therapy
1) ECT
SA barbiturate, general anesthesia, an anticholinergic agent, succinylcholine
treatment-resistant depression
severe depression in pregnancy
severe vegetative depression
psychotic depression
frequency of ECT treatments ?
Lithium ?

12. 2) Psychotherapy
• mild-to-moderate depression
3) Lifestyle Adjustments
Alcohol and illicit drug
Sleep habits
Dietary factors
Increased physical activity
4) Repetitive transcranial
magnetic stimulation (rTMS)
5) Vagus nerve stimulation (VNS)
6) phototherapy
Non-Pharmacologic therapy

13. TMS
VNS
Non-Pharmacologic therapy

14. 1) Serotonin Syndrome
 SSRI,MAOI: SNRI, TCA,anti-migraine, anti-emetic, Illicit drugs, opioid, lithium, linezolid, ritonavir
 Treatment? (4)
2) SSRI Discontinuation Syndrome (FINISH)
Flulike symptoms (fatigue, lethargy, myalgias, chills, headache)
Insomnia (sleep disturbances, vivid dreams)
Nausea (gastrointestinal symptoms, vomiting, diarrhea)
Imbalance (dizziness, vertigo, ataxia)
Sensory disturbances (sensation of electric shocks in the arms, legs, or head)
Hyperarousal (anxiety, agitation)
3) SSRI-Induced Sexual Dysfunction
 Premature ejaculation ?
 Drug holiday (Viagra, Amantadine, buspirone, yohimbine)
4) ADE and Interactions of SSRIs
1. SSRI

15. Dose SSRI
5-HT syndrome
Interactions CYP450

16. Paroxetine
Citalopram Fluvoxamine
fluoxetine
Sertraline

17. 2. SNRI
Pain (neuropathic)
Anxiety disorder
Venlafaxine
Migraine
Narcolepsy
Duloxetine
Stress Urinary incontinence
Milnacipran vs levomilnacipran
Duloxetine
Milnacipran

18. 3. 5-HT modulators
Vilazodone (SPARI)
Vortioxetine
Trazodone (SARI)
Insomnia
Nefazodone (SARI)
Priapism ?
Vortioxetine

19. 4. TCA
Pain (neuropathic, …)
Anxiety Disorder
Imipramine
Childhood Enuresis
Desipramine
IBS
Amitriptiline
Migraine
IBS
Sialorrhea
Nortriptiline
Smoking cessation

20. TCA: ADE
Histamine 1
Muscarinic 1
Alpha 1
Na Channel

21. 5. MAOI
 Switch serotonergic to MAOI
 The dietary tyramine interaction
 Drug–Drug interactions for MAOIs

22. MAOI:
Food
and
Drug
interactions

23. 6. Miscellaneous
agents
Mirtazapine (α2)
tension headache
H1 ADE
Agomelatine
Bupropion (NDRI)
Seasonal disorder
Smoking cessation
Sexual dysfx SSRI
ADHD
Seizures
NRI (ADHD)
L-5-Methyltetrahydrofolate
S-adenosyl-methionine (SAMe)
Omega-3 fatty acids
St. John’s wort

24. Esketamine (March 5, 2019)
ADE
CSN: Depersonalization, derealization, dissociative reaction,
sedated state, dizziness, vertigo, headache, hypoesthesia,
anxiety, lethargy
CV: increase BP
GI: Nausea, vomiting
Dose
INDUCTION PHASE:
Weeks 1 to 4:
-Day 1: 56 mg intranasally once
-Subsequent doses: 56 to 84 mg intranasally 2 times a week
MAINTENANCE PHASE:
Weeks 5 to 8: 56 to 84 mg intranasally once a week
Weeks 9 and after: 56 to 84 mg intranasally every 2 weeks
OR once a week
Esketamine

25. Brexanolone (March 19, 2019)

26. 1. Evidence-based selection
2. Symptom-based selection
How to choose an antidepressant ?

27. Symptom-based
antidepressant
selection

29. Dosage
Ranges
of
Commonly
Prescribed
Antidepressant
Medications

30. Case
(86-1)

31. Case
(86-1)
 all antidepressants are considered equal, regardless of class
 Sertraline & escitalopram have the best efficacy to
safety/tolerability ratio

32. Case
(86-1)