Biological Therapies in Psychiatry

Dr. Vishal DhimanAssoc. Professor

Dept. of Psychiatry AIIMS Rishikesh

Why Biological approach?

• Neuropsychiatric disorders are:• Common• Highly disabling• Financial burden

• Bio-psycho-social model of illness management

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What biological approach?

•Pharmacology• Neuromodulation

• ECT• MST• TMS• tDCS• Vagus nerve stimulation (VNS)• Deep brain stimulation (DBS)

Brain stimulation vs Psychopharmacology

*Table copied from Comprehensive Textbook of Psychiatry 10th ed. for purpose of small group teaching only

Neuromodulation: MOA

• Circuit based models of psychiatric illnesses

• Neuromodulation modifies activity in circuit

• Specific target points obscured

Various Neuromodulation Approaches

1. ECT2. MST3. TMS4. tDCS5. Vagus nerve stimulation (VNS)6. Deep brain stimulation (DBS)

Electroconvulsive Therapy

• Cerletti and Bini in 1938

• Downwards trend of ECT in 1970s

• Subsequently significant modifications in the ECT techniques

• Very safe modality

Electroconvulsive Therapy

• APA Council on R & D - ECT Task Force – 1974

• APA Task Force - Report on ECT 1990

• Latest guidelines - 2001

Indications

qMajor severe depression• With suicidal risk • With stupor• With poor intake of food and fluids• With melancholia

• With psychotic features• With unsatisfactory response to drug therapy• Where drugs are contraindicated, or have serious side effects• Where speedier recovery is needed.

*Undergraduate’s textbook of Psychiatry by Neeraj Ahuja

Indications

•Severe catatonia (non-organic)•With stupor•With poor intake of food and fluids•With unsatisfactory response to drug therapy•Where drugs are contraindicated, or have serious side-

effects.•Where speedier recovery is needed.

*Undergraduate’s textbook of Psychiatry by Neeraj Ahuja

Indications

•Severe psychoses• With risk of suicide, homicide or danger of physical assault

•With unsatisfactory response to drug therapy

•Where drugs are contraindicated, or have serious side

effects

•With very prominent depressive features (e.g. schizo-

affective disorder).

*Undergraduate’s textbook of Psychiatry by Neeraj Ahuja

Contraindications

• Absolute• Raised intracranial tension

• Relative• Recent myocardial infarction (MI)• Severe hypertension• Cerebrovascular accident (CVA)• Severe pulmonary disease• Retinal detachment• Pheochromocytoma.

*Undergraduate’s textbook of Psychiatry by Neeraj Ahuja

ECT - Types

• Direct

• Modified

• Unilateral

• Bilateral

• Brief

• Ultra-brief

ECT - Side Effects and Risks

• Side effects associated with GA

•Mortality rate is 1:10,000 patients

•Memory disturbances (both anterograde and retrograde)

*Undergraduate’s textbook of Psychiatry by Neeraj Ahuja

Magnetic Seizure Therapy

• Seizure induction by high frequency magnetic stimulation

• No skull resistance

• Better control over the site of seizure onset

• No direct spread of current to subcortical brain regions

• Earlier - 40-60 Hz stimulation

• Increased stimulator capacity - 100 Hz

• Efficacious as antidepressant

Transcranial Magnetic Stimulation (TMS)

• Michael Faraday (1838)

• Barker (1985), University of Sheffield in the UK

• “Electrode-less electric stimulation of the brain via

electromagnetic induction”

rTMS

• Early stimulators - less than 0.3 Hz

• Single-pulse TMS

• Large round coils - lacked the focality

• Rx of depression and schizophrenia

• Subsequent devices - higher repetitive rates up to 20 Hz

rTMS: MOA / effects

• Acute effects• Phasic activation of neural circuits

• Prolonged effects• Neuroplasticity

► Changes in synaptic efficacy akin to long-term potentiation or depression► Alteration in neurotropic factors►Modulation of cortical excitability►Modulation of functional connectivity

*Ref: Comprehensive Textbook of Psychiatry 10th ed.

rTMS - MOA

• Depression: left dorsolateral prefrontal cortex underactive c.f. right

DLPFC

• High frequency rTMS (10 Hz) activates the cortex

• Low frequency rTMS (1 Hz) inhibits the cortex

• Restores L-R symmetry

• Produces antidepressant effect

rTMS: Clinical application in Neuro-Psychiatry

1) Refractory depression2) Rx of specific symptoms or syndromes of schizophrenia,

especially:• Negative symptoms • Auditory verbal hallucinations

3) Other (less proven) indications in schizophrenia include:• Cognitive deficit • Catatonic symptoms• Obsessive-compulsive symptoms• Comorbid nicotine abuse (through the decrease of craving)

4) OCD5) Autism, Tic disorder, Tinnitus, Parkinson’s disease,

movement disorders, etc.

Safety: rTMS

• Seizure is the most serious side effect – risk less than 0.1%

• Safety aspects of the instrument needs to be remembered

• Risk Increased: Stimulants, Neurological condition, sleep

deprivation

Transcranial Direct Current Stimulation (tDCS)

• tDCS - 1960s•weak constant current via scalp (1-2mA) using surface

electrodes• clinical improvement similar to antidepressant medication• Recent revival of technique• Safe to use• No risk of seizures• No cognitive side effects• Compact technology• Easy to administer• Relatively cost effective

Vagus nerve stimulation (VNS)

• George and colleagues – 2000

• Direct, intermittent electrical stimulation

• Left cervical vagus nerve

• Implanted pulse generator

• Battery/generator usually implanted subcutaneously in the left chest wall

• Approved for treatment resistant epilepsy

• FDA approval for chronic, TRD as an adjunctive therapy – 2005

Deep Brain Stimulation

• Nuttin and colleagues

• Intractable OCD

• Placement of small brain “leads” with multiple electrode contacts

into subcortical nuclei or specific white matter tracts

• Burr holes in skull bone under local anesthesia

• Guided by multimodal imaging and stereotactic land-marking

• Subdermal pacemaker implanted

DBS

Uses:

• Parkinson's Disease

• Tourette syndrome

• OCD

• Depression

Thankyou!

vishal.psyc@aiimsrishikesh.edu.in