TR OCD

Treatment Resistant OCD

Failure to achieve ≥35% reduction in Y-BOCS despite ≥3 adequate SRI trials (including clomipramine) at maximum tolerated doses for ≥12 weeks each + adequate ERP therapy (10–20 sessions)

Percentage of OCD patients truly treatment resistant

10–20% truly resistant; 40–60% partially resistant

Scale measuring OCD severity and treatment response definition

Y-BOCS (Yale-Brown Obsessive Compulsive Scale); ≥35% reduction = response; scores: mild

Hyperactive brain circuit in OCD

CSTC loop — Cortico-Striato-Thalamo-Cortical loop

Role of Orbitofrontal Cortex in OCD

Generates false alarm 'something is wrong' error signals → hyperactive in OCD → drives compulsions

Role of Caudate Nucleus in OCD

Normally filters/gates OFC signals; in OCD, it is overactive and fails to suppress false alarms. SSRIs and ERP reduce caudate hyperactivity.

Reason OCD treatments require higher SRI doses than depression

Need to significantly reduce OFC hyperactivity; OFC modulation requires higher serotonergic tone than mood circuits.

How ERP breaks the CSTC loop

Prevents compulsion → brain learns the alarm is false → loop extinguished through habituation/extinction learning.

Step 1 in OCD management

ERP + SSRI at OCD doses; minimum 12 weeks; mild-moderate: ERP alone; moderate-severe: ERP + SSRI.

Step 2 in OCD management

Optimise SSRI to maximum tolerated dose for ≥12 weeks.

Step 3 in OCD management

Switch SSRI or start Clomipramine (most potent anti-OCD drug) + intensify ERP.

Step 4 in OCD management

Augment SRI with low-dose antipsychotic (risperidone first choice) ± D-cycloserine.

Step 5 in OCD management

Somatic therapies — inhibitory TMS over SMA/OFC, ECT for severe comorbid depression.

Step 6 in OCD management

DBS — FDA approved (HDE) for TRO; targets ALIC or nucleus accumbens; 50–60% response rate.

OCD dose of Fluoxetine vs Depression dose

OCD: 40–80mg | Depression: 20–40mg

OCD dose of Fluvoxamine vs Depression dose

OCD: 200–300mg | Depression: 100–150mg

OCD dose of Sertraline vs Depression dose

OCD: 150–200mg | Depression: 50–100mg

OCD dose of Escitalopram vs Depression dose

OCD: 20–40mg | Depression: 10–20mg

OCD dose of Clomipramine and its uniqueness

150–250mg; most potent anti-OCD drug; TCA with superior serotonin selectivity; risks: QTc prolongation, arrhythmia, seizures, anticholinergic effects.

Mnemonic for OCD SRI drugs

FFSEPV — Fluoxetine, Fluvoxamine, Sertraline, Escitalopram, Paroxetine, Venlafaxine (+ Clomipramine = most potent TCA).

SSRI with QTc risk in high doses

Citalopram — QTc risk above 40mg; avoid high-dose use in OCD.

Antipsychotic with best evidence for OCD augmentation

Risperidone 0.5–2mg/day — best evidence; especially with comorbid tics or schizotypy.

Order of antipsychotic augmentation evidence in TRO

Risperidone > Aripiprazole > Quetiapine > Haloperidol (Haloperidol especially for OCD + Tourette's).

Role of D-cycloserine in OCD

NMDA partial agonist; given 50–100mg, 1 hour before ERP session; enhances extinction learning; augments therapy not the drug effect.

Role of Riluzole in TRO

Glutamate modulator; small trials show reduction in OCD severity; targets CSTC glutamate hyperactivity.

Use of N-acetylcysteine (NAC) in OCD

Glutamate modulator + antioxidant; some evidence especially in grooming-related OCD (trichotillomania); dose 600–3000mg/day.

TMS target and frequency in TRO

Low-frequency (1Hz) inhibitory rTMS over right SMA (supplementary motor area) or DLPFC; FDA approved for OCD 2018; 20–30 sessions.

DBS targets in TRO and approval status

ALIC (anterior limb of internal capsule), nucleus accumbens, STN; FDA humanitarian device exemption (HDE) approved; 50–60% response; reversible.

Anterior capsulotomy

Surgical or Gamma Knife ablation of ALIC; irreversible; 30–65% response; reserved for ultra-refractory; risks include cognitive blunting and personality change.

Anterior cingulotomy

Ablation of anterior cingulate cortex; reduces error signalling; 30–50% response; may cause personality change.

Investigation before high-dose Clomipramine

ECG (QTc monitoring) + EEG (seizure threshold reduced >250mg) + serum clomipramine + desmethylclomipramine levels.

Raised desmethylclomipramine level indicates

Increased seizure risk — active metabolite accumulation.

PANDAS and its connection to OCD

Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections; autoimmune attack on basal ganglia → sudden-onset OCD in children; investigate with ASO titre + MRI brain.

Treatment of PANDAS-OCD

Treat infection (penicillin) + IVIG or plasmapheresis + SSRI + ERP.

Good prognostic factors in TRO

Good insight, low Y-BOCS, contamination/checking subtype, clear precipitant, no personality disorder, good ERP completion, strong social support.

Poor prognostic factors in TRO

Poor insight, high Y-BOCS, symmetry/hoarding/intrusive thought subtype, comorbid depression/tics/schizotypy, PANDAS, multiple failed SRI trials, avoidance of ERP.

OCD classification in DSM-5

Own chapter — 'OCD and Related Disorders' (moved out of Anxiety Disorders in DSM-5 2013).

Insight specifier added in DSM-5 for OCD

Good/fair insight, poor/absent insight, delusional beliefs — poor insight OCD may respond better to antipsychotic augmentation.

Related disorders grouped with OCD in DSM-5 and ICD-11

BDD, hoarding disorder, trichotillomania, excoriation disorder.