DEPRESSION – TREATMENT

Treatment modalities:

• Pharmacotherapy.
• Psychotherapy.
• Other somatic treatments.

1. Pharmacotherapy:

 Considerations:  

• All available antidepressants takes 3-4 weeks to exert significant therapeutic effect.
• Usage of specific pharmacotherapy doubles chances for recover within 1 month.
• All available antidepressants have similar profile except adverse effects.
  • Choice of drug also depends on their adverse effects.

Duration of therapy:

• Antidepressant treatrnent should be maintained for atleast 6 months or equal to duration of previous episode, whichever is greater.
• Prophylactic antidepressant treatment is effective in reducing number & severity of episodes.
  • Should be given to patients who have had 3 or more prior depressive episodes or in chronic major depressive disorder (> 2 years duration).

Drugs used – 

Tricyclic and tetracyclic antidepressants (TCAs):

• 1st class of antidepressants used.
• MOA: 
  • Primary action – Acts by blocking serotonin & norepinephrine transporters —> Increases neurotransmitters levels in synapses.
  • Secondary action– Antagonism of muscarinic, histaminic H1, α1 & , α2 adrenergic receptors & cardiac sodium channels bloackage. 
    • Responsible for their side effect.
• Drugs included: 
  • lmipramine, desipramine, trimipramine, amitriptyline, nortriptyline, protriptyline, amoxapine, doxepin, maprotiline & clomipramine.
  • Clomipramine – Most serotinin selective drug.
  • Desipramine – Most norepinephrine selective drug.
• Adverse effects: 
  • Anticholinergic side effects (constipation, urinary retention), cardiac arrhythmias, hypotension & seizures (Sodium channel bloack in heart & brain), & sedation.
• Contraindications: 
  • Glaucoma, prostate hypertrophy, 

Selective serotonin reuptake inhibitors (SSRIs):

• Most commonly prescribed antidepressants.
• Lesser adverse effects.
• DOC for depression, obsessive compulsivel disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder & phobia.
• MOA: Acts by blocking serotonin reuptake.
• Drugs included: Fluoxetine, fluvoxamine, citalopram, escitalopram, sertraline, paroxetine, vortioxetine, & vilazodone.
• Adverse effects: Nausea (most common) –> anxiety & diarrhoea.
• Vortioxetine: 
  • Recent antidepressant.
  • MOA: Serotonin reuptake inhibitor. agonism at 5-HT1A receptor, partial agonism at 5-HT1B receptor & antagonism at 5-HT3. 5-HT1D & 5-HT7 receptors.

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors):

• MOA: Blockade of neuronal serotonin & norepinephrine uptake transporters.
  • Hence,“dual reuptake inhibitors”.
• Drugs included:Venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran.

Monoamine oxidase inhibitors:

• MOA: Inhibits monoamines enzyme (MAO-A & MAO-B) metabolism.
• Drugs included: Non-selective MAO inhibitors – Tranylcypromine, phenelzine & isocarboxazid.

Atypical antidepressants:

• Drugs included: 
• SARI (serotonin antagonist & reuptake inhibitors): Trazodone & nefazodone.
• NSSA (nor adrenergic and specific serotonergic antidepressant): Mirtazapin.
• NDRI (norepinephrine-dopamine reuptake inhibitors): Bupropion – Inhibition of norepinephrine & dopamine reuptake.
• Serotonin reuptake enhancer: Tianeptine & amineptine – Acts by enhancing serotonin reuptake.
• Antipsychotics: In patient with depression & psychotic symptoms.

2. Psychotherapy:

Techniques used:

• Cognitive behavioral therapy:
  • Aims at correcting cognitive distortions (faulty ways of thinking) & faulty behaviors.
  • Most effective psychotherapeutic technique for depression.
• Interpersonal therapy.
• Other therapies: 
  • Behavior therapy, family therapy & psychoanalytically oriented therapy.

3.  Other somatic treatments

• Electroconvulsive therapy (ECT): 
• Indications: 
  • Severe depression with suicide risk.
  • Severe depression with stupor.
  • Depression with psychotic symptoms
  • Refractoriness to other treatment modalities.
• Transcranial magnetic stimulation:
  • Newer modality using magnetic energy.
  • Nonconvulsive.
  • Not requires anesthesia.
  • Lesser side effects.
• Vagal nerve stimulation.
• Deep brain stimulation – 
  • Used for chronic & intractable depression.