3. DEPRESSION
• MOOD
• Physical and cognitive symptoms
• NOT JUST BEING SAD !!!
• >15%
• TYPES
• Psychotic major depression
• Major depression with atypical feature
• Melancholic major depression
• Seasonal affective disorder
• Major depression with peripartum onset
• DISABILITY
• MORTALITY
• UNDERDIAGNOSED
• UNDERTREATED
• CO MORBID CONDITIONS
12. TRICYCLIC ANTIDEPRESSANTS
Neuronal block of SERT/NET/DAT
Inhibit the re-uptake of 5HT/NE/DA
Increased concentration in the synaptic cleft.
3-4
weeks
H1
Ach
α2 Adr
14. ADVERSE EFFECTS
• Sedation,orthostatic hypotension
• Blurred vision, dry mouth, tachycardia,
constipation, difficulty urinating
• Weight gain
• Quinidine-like effects
• Lower the seizure
threshold.
DRUG INTERACTIONS
• Drugs that inhibit CYP2D6, such as
bupropion and SSRIs
• Shouldn’t be used within 14days of
MAOI
• Antipsychotic agents, type 1C
CHOLINERGIC
REBOUND
15. MONOAMINE OXIDASE INHIBITORS
• MAO-A and MAO-B 5HT,DA
• EXOGENOUS- TYRAMINENE
• 3rd line drugs
NE
HYPERTENSIVE
CRISIS
1.Tranylcypromine
2.Phenelzine
3.Isocarboxazid.
4.Selegiline
5.Moclobemide
6.Eprobemide,
17. SELECTIVE SEROTONIN REUPTAKE
INHIBITORS
• 1st drug fluoxetine available in 1988
Inhibits SERT
AUTORECEPTOR
MECHANISM
5HT1A and 5HT7
autoreceptors reduces 5HT
synthesis and release
Increase in cAMP signalling
Phosphorylation of the
nuclear transcription factor
CREB
>Expression of BDNF
>Inc neurogenesis in
hippocampus and
subventricular zone
19. • Insomnia,irritability
• Nausea, Diarrhoea,emesis – 5HT3
• Akathisia , extrapyramidal symptoms
• Affect platelet serotonin
• Sertraline and citalopram - safest when used
with warfarin
• Sexual – dec.
libido,
erectile
dysfunction,a
norgasmia,ej
aculatory
delay –
5HT2
• Oral PDE-5
inhibitors ( sildenafil,
25–50 mg; tadalafil,
5-20 mg; or
vardenafil, 10–20
mg taken 1 hour
prior to sexual
activity)
• Bupropion (75–150
mg orally daily)
Cyproheptadine, 4
mg orally prior to
sexual activity,
DRUG HOLIDAY
20. • Initial dose -typically a therapeutic dose
• lower lethality in overdose compared to TCAs or
MAO inhibitors.
• Shorter t1/2rapid aborting of A/E
• SEROTONIN SYNDROME +TCA/MAOI
• The SSRIs should not be started until at least 14
days following discontinuation of treatment with
an MAOI; this allows for synthesis of the new
MAO
21. SEROTONIN NOREPINEPHRINE
REUPTAKE INHIBITORS
• Both NET and SERT
• VENLAFAXINE – 5(11) HRS
• DULOXETINE- 12 hrs
• CYP2D6,3A4
USES
• Depression,Anxiety,
• Fibromyalgia and
neuropathic pain
• Off-label
• Stress urinary
incontinence
(duloxetine)
• Autism
• Binge-eating
disorders, hot flashes
• PTSD (venlafaxine)
SEROTONIN SYNDROME
WASHOUT PERIOD
ADVERSE EFFECTS
• Nausea, constipation,
insomnia, headaches, sexual
dysfunction.
• DIASTOLIC
HYPERTENSION-Venlafaxine
• BLEEDING- Milnacipran
22. SEROTONIN RECEPTOR ANTAGONISTS
• Trazodone,Nefazadone,Vilazadone Blocks 5HT2
and α1 adrenergic receptors.
• Mirtazapine and mianserin- H1> 5HT2A,
5HT2C, and 5HT3
• Vortioxetine - potent SERT inhibitor
partial agonist at 5HT1A, 5HT1B
Antagonist at 5HT1D, 5HT3, and 5HT7 receptors
PHARMACOKINETICS
MIRTAZIPINE 16-30
hrs
TRAZADONE 6 hrs
NEFAZADONE 2-4 hrs
24. BUPROPION
• Inhibition of DAT and NET
• Hydroxybupropion
• T1/2- 21 hrs
• CYP2B6
• Cautious in renal and hepatic impaired
• EXTENDED RELEASE
25. BUPROPION
• ADVERSE EFFECTS
• Anxiety, mild
tachycardia,
hypertension,
irritability, and
tremor.
• Headache, nausea, dry
mouth, constipation,
appetite suppression,
insomnia,
• Aggression,
impulsivity, and
agitation
• Seizures -dose and
Cp, (>450 mg/day)
.
• USES
• Depression
• Seasonal depressive
disorder,
• Smoking cessation
treatment
• ADHD
• Off label-
neuropathic pain
and weight loss
26. ATYPICAL ANTIPSYCHOTICS
• Aripiprazole or Quetiapine
• Olanzapine and the SSRI fluoxetine
• Treatment resistant depression
• Combined with SSRI and SNRI
FDA
27. STIMULANTS AND OTHER DRUGS
• Dextroamphetamine
(5–30 mg/day orally)
and methylphenidate
(10–45 mg/day orally)
- short-term
treatment in medically
ill and geriatric
patients.
• Rapid onset of action
(hours)
• tachycardia, agitation
• two divided doses early
• Intravenous infusion of
the dissociative
anesthetic ketamine
• . The effects of a single
treatment are short-
lived (about 3–7 days
• NMDA antagonists -
28. RECENT DRUGS
• Esketamine intranasal
• Noncompetitive NMDA receptor antagonists -
memantine, dextromethorphan/quin idine,
dextromethorphan/bupropion, and lanicemine),
• NR2B subunit-specific NMDA receptor antagonists
(traxoprodil, MK-0657),
• NMDA receptor glycine site partial agonists (D-
cycloserine, rapastinel),
• metabotropic glutamate receptor (mGluR)
antagonists (basimglurant, declogurant)
Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L,
Manji HA, Drevets WC: Efficacy and safety of intranasal esketamine adjunctive to oral
antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA
Psychiatry 2018; 75: 139–148.
29.
30. The American Psychiatric Association (APA)
Practice Guideline for the Treatment of
Patients with Major Depressive Disorder(2011)
• .CUSTOMIZATION
• Hamilton or Montgomery-Asberg clinician-administered
rating scales or the self-administered Patient Health
Questionnaire
• Columbia-Suicide Severity Risk Scale
Clinical assessment
Reactions to
previous treatment
Patient preference
Stressors
Presence of other
disorders
31. DIFFERENTIAL DIAGNOSIS
• Schizophrenia, partial complex seizures,
organic brain syndromes, panic disorders,
and anxiety
• Thyroid dysfunction and other
endocrinopathies
• Malignancies, including central and
gastrointestinal tumors
• Strokes, particularly dominant hemisphere
lesions
• Medication-induced depressive symptoms
32.
33. • Lag 2–12 weeks
• SATISFACTORYcontd for 6-12 months
• Indefinite fixed dose
SWITCHING OVER
• Adequate washout – atleast 2 weeks
• Not required if of the same group
• If Antipsychotics look for body mass index,
lipids, and glucose
• 1st episode at
<20/>50 age
• 2 episodes >40
• 3 episodes –
any age
• Chronic
depression >2
yrs
34. TAPERING
• Over several weeks.
• counseled about the potential for relapse,
• plan should be established for seeking treatment
if symptoms recur.
• Patients should be monitored for several months
35.
36. TREATMENT
RESISTANT
DEPRESSION
The STAR*D
1. switch to a second agent that may be from the same or
different class of antidepressant
2. Augmentation with
a. Bupropion (150–450 mg/day),
b. Lithium (eg, 300–900 mg/day orally),
c. Thyroid medication (eg, liothyronine, 25–50 mcg/day
orally)
d. Second-generation antipsychotic (eg, aripiprazole [5–15
mg/day] or olanzapine [5–15 mg/day]).
37. • PREGNANT
1. Psychotherapy
2. ECT and BRIGHT LIGHT
THEARAPY
SSRI – Persistent Pulmonary
hypertension
Neonatal withdrawal
symptoms
POST PARTUM DEPRESSION
• 1st episodes of depression-,
6-12 months
• Recurrent major depression
following pregnancy, long-
term maintenance
treatment with an
antidepressant
38.
39.
40. REFERENCES
• The Pharmacological basis of therapeutics,Goodman and
Gilman, 13 th edition
• Current Medical Diagnosis and Treatment ,2019
• Basic and Clinical Pharmacology,Katzung,14th edition
• Gabbards treatment of Psychiatric disorders
• American Psychiatric Association Guidelines
