Anti depressants

Anti-Depressants

Dr.Harim Mohsin

First things first


Depression is a medical condition & not any fault of the
individual concerned.



Assessment & evaluation is mandatory-Severity, etiology
& risk-factors.



Treatment plan comprises of medication, psychological &
social support.

Indications


Depression
Moderate-Severe, Atypical, SAD, Depressive episode of
Bipolar disorder.



Anxiety disorders
GAD, Panic Disorder, Social Anxiety, Adjustment disorders,
Agoraphobia, OCD, PTSD.

Mode of action
All antidepressants function by increasing availability
of monoamines (5-HT, NA or DA) by one of the
following methods:


Presynaptic inhibition of reuptake of 5-HT, NA or DA.



Antagonist activity at presynaptic inhibitory 5HT or NA
receptors which enhances neurotransmitter release.



Inhibition of Monoaminase oxidase, reducing NT
breakdown.



Increasing availability of NT precursors.

Initial resolution of depressive symptoms takes minimum
of 2-4 weeks.

Classification
Broadly into 2 Types:
 Re-uptake

Inhibitors
 Enzyme Inhibitors

Classification


Selective serotonin reuptake inhibitors
(SSRIs)

Monoamine oxidase inhibitors (MAOIs)
–
–



Serotonin-norepinephrine reuptake
inhibitors (SNRIs)

Irreversible
Reversible




Norepinephrine reuptake inhibitors
(NRIs)



Tricyclic antidepressants (TCAs)



Norepinephrine-dopamine reuptake
inhibitors (NDRIs)



Serotonin antagonist and reuptake
inhibitors (SARIs)

Noradrenergic and specific serotonergic
antidepressant (NaSSA)



Tetracyclic antidepressants (TeCAs)

SSRIs (Selective serotonin reuptake inhibitors)
Mechanism: Increases 5HT in synaptic cleft.


Citalopram (Cipram)



Escitalopram (Cipralex, Citanew, Neolexa)



Paroxetine (Paroxin, Seroxat)



Fluoxetine (Prozac, Depex)



Fluvoxamine (Faverin)



Sertraline (Zoloft, Sert):

Indications
 Depression
 Panic

Disorder with agoraphobia
 Social Anxiety/ GAD/ OCD
 Bulimia
 PTSD

Side-effects









GI discomfort/ nausea
Sexual dysfunction
Sleep disturbance
Dry mouth
Tremor
Headache
Anxiety/ restlessness.
Fatigue

Caution:
 Be aware of
interactions-inhibitory
effects on P450 &
changes with alcohol,
anticoagulants, MAOIs,
TCA, smoking etc.

TCA Mechanism
Mechanism:
 Reuptake inhibition
NA, 5HT & DA.

TCAs (Tricyclic antidepressants )
 Amitriptyline

(Tryptanol)
 Clomipramine (Clomfranil)
 Desipramine (Norpramin,Pertofrane)
 Dosulepin (Prothiaden)
 Doxepin (Doxin)
 Imipramine (Tofranil, Imidol)
 Nortriptyline (Sensival)

Indications
 Depression
 Nocturnal

Enuresis (Amitriptyline/
Imipramine)

 Phobic/Obsessional
 Cataplexy

States

with narcolepsy

Side-effects








Dry mouth,
Caution:
Blurred vision,
 Arrhythmias & ECG
Sedation,
changes. Monitor
Orthostatic hypotension,
Cardiac function, LFTs,
Constipation,
UCEs.
urinary incontinence.
Disorientation or
 Should be used
confusion
cautiously in elderly.

SNRIs (Serotonin-norepinephrine reuptake
inhibitors )
Mechanism: Similar to SSRI, Inhibit 5HT & NA (high doses DA)
Indications: GAD, Depression.


Venlafaxine (Efexor)



Duloxetine (Oxcym DR, Hapibar, Lyta)



Levomilnacipran (Fetzima)



Tramadol (Tramal, Ultram)



Sibutramine (Meridia, Reductil)

Side-effects: Similar to SSRIs & may cause HTN.

MAOIs (Monoamine oxidase inhibitors)




Irreversible inhibition of MAO-A
(acts on NA, DA, 5HT & Tyramine) &
MAO-B (acts on DA, Tyramine,
Phenylethylamine, benzylamine)
leading to accumulation of
monoamines in Synaptic Cleft.

 RIMAs: Reversible inhibition
of MAO-A.

Indications
 Depression

(atypical)



Parkinson's Disease,



Migraine prophylaxis



Other disorders: panic disorder with agoraphobia,
social phobia, bulimia, PTSD, borderline personality
disorder, and bipolar depression.

MAOIs (Monoamine oxidase inhibitors)
Irreversible
 Isocarboxazid (Marplan)
 Phenelzine (Nardil)
 Selegiline (Selgin, Eklin)
Reversible
 Moclobemide (Aurorix,
Manerix)
 Pirlindole (Pirazidol)

Side-Effects


Hypertensive crisis



Dizziness/ Headaches



Hepatotoxicity



Sleep disturbance



Weight gain



Sexual dysfunction



Drug Interactions

Caution:
 Dietary restriction
(Tyramine) e.g: cheese,
chocolate, wine, beans &
soy products.


Serotonin Syndrome: Lifethreatening condition with
somatic, autonomic &
cognitive effectsTachycardia, myoclonus,
tremors, altered Mental
status, hyperthermia, DIC,
metabolic disturbances.

Tetracyclic antidepressants (TeCAs)
Mode: Similar to TCA without anticholinergic SE
Indications: TCA with sedation.
S/E- Cardiotoxicity





Mirtazapine (Remeron)
Mianserin (Bolvidon, Norval, Tolvon)
Amoxapine (Asendin)
Maprotiline (Ludiomil)

Noradrenergic and specific serotonergic antidepressant (NaSSA)
Mode: α2 inhibitor (^NA/5HT), 5HT1, 5HT2 antagonist.
Indications: Depression (+anxiety,wt loss) adjunct SSRI/venlafaxine to improve
SxD, GI discomfort.
Advantages: Low Toxicity, less sexual dysfunction & GI upset.

(SARIs)

Serotonin antagonist and reuptake inhibitors
Mode: 5HT reuptake inhibitor & antagonist.
(sedation/ antihistamine)
Indication: Depression (+insomnia) / Anxiety
Advantage: Less antimuscranic/ cardiotoxic than TCA.
 Trazodone

(Deprel)
 Etoperidone (Axiomin, Etonin)
 Nefazodone (Serzone, Nefadar)

Other anti-depressants


Norepinephrine-dopamine reuptake inhibitors (NDRIs)

Mode: NA/DA reuptake inhibition
Indications: Depression (with marked psychomotor retardation or hypersomnia),
Nicotine/stimulants dependence, ADHD.
Advantage: Unusual mode of action-alerting effects, controls impulse disorders &
secondary benefits as AD.
S/E: Seizures & hypersensitivity.


Bupropion (Wellbutrin, Zyban)

Other anti-depressants


Norepinephrine reuptake inhibitors (NRIs)-

Indication: Atypical Depression

Reboxetine (Edronax)

Adjunctive treatments
Itself doesn’t possess antidepressant quality but works in combination.
Atypical antipsychotics
 Aripiprazole (Aripip)
 Olanzapine (Olanzia,Amprexa)
 Quetiapine (Qusel)
 Risperidone (Risperdal,Persch, Neoris)






Others
Carbamazepine
Lamotrigine (Lamictal)
Lithium salts
Triiodothyronine (T3; a thyroid hormone)

Alternate treatments
Psychotherapy / counseling
 Phytotherapy: St-John’s Wort
 Exercise
 Nutritional Supplements- Vitamins, minerals, O3-FA.
 Adequate sleep.
 Avoid Alcohol & other recreational drugs
 Meditation, Acupuncture, chiropractice & yoga.


Anti depressants

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