Dr Yong Mo Juin. Consultant. GP Symposium 23rd April 2016

Transcription

1 Dr Yong Mo Juin Consultant GP Symposium 23rd April 2016

2 Prevalence rate: 2-3 % in general population Significant impact on human, social functioning, quality of life, family relationships and socioeconomic status Most OCD individuals spend an average of 17 years before receiving appropriate dx and Rx for their illness World Health Organization: OCD among the 10 most disabling illnesses National Comorbidity Survey: OCD is the anxiety disorder with the highest percentage (50-60%) of serious cases

3 Used extensively in research, clinical practice Reliable and valid measure To determine severity of OCD and monitor improvement during treatment Clinician rated, 10 item scale Each item rated from 0 (no symptom) to 4 (extreme) Score ranges from 0 to 40: 0 to 7 subclinical 8 to 15 mild 16 to 23 moderate 24 to 31 severe 32 to 40 extreme

4 According to several recent treatment guidelines: Serotonin reuptake inhibitors (SRIs) Cognitive behavioral therapy (CBT): exposure and response prevention (ERP) and/or cognitive restructuring Combination of SRI and ERP

5 Selective Serotonin Reuptake Inhibitors (SSRIs): First-line for OCD treatment Illness is biologically based, respond well to potent serotonin reuptake inhibitor Well-tolerated Favorable safety profile, not life-threatening in overdoses

6 Fluoxetine* (Prozac) Fluvoxamine* (Luvox) Sertraline* (Zoloft) Paroxetine* (Paxil) Citalopram (Celexa) Escitalopram (Lexapro) These medications with * have FDA approval for treatment of OCD

7 Most SSRIs have randomized clinical trials to support their use in OCD Need at least a few weeks to see a response Dose-response relationship for SSRI treatment in OCD; higher doses typically required to achieve response or remission

8 Compound SRI Starting dose (mg/day) Usual target dose (mg/day) Usual maximum dose (mg/day) Fluoxetine Fluvoxamine Sertraline Paroxetine Citalopram Escitalopram Clomiprami ne

9 During acute phase: Nausea, dry mouth, diarrhea and other GI symptoms Reduced appetite, weight loss Excessive sweating Tremor, headache, flushing Insomnia, sedation Anxiety, agitation, jitteriness

10 Common side effects during acute phase Typically in more than 10 % May need to start at half of the starting dose or less Dividing the dose of the SSRI could be an option

11 Weight gain Fatigue, sleep disturbances Cognitive and memory symptoms (diminished working memory, cognitive slowing, wordfinding difficulty) Sexual Dysfunction

12 SIADH with hyponatremia Hyperprolactinemia, galactorrhea Bruxism, hair loss Prolonged bleeding time, abnormal bleeding due to platelet dysfunction Reports of upper GI bleeding when SSRIs were combined with NSAIDs

13 40-60% of OCD patients do not respond adequately to first-line SRI therapy An greater proportion of patients fail to experience complete remission of their symptoms after an adequate first trial An adequate trial: at least 12 weeks with moderate-high dosages of SRIs

14 Proposed by the International Treatment Refractory OCD Consortium: Full response: 35% or greater reduction of Y-BOCS Partial response: 25% or greater but less than 35% reduction of the Y-BOCS Non-response: Less than 25% Y-BOCS reduction Recovery: Complete and objective disappearance of symptoms; Y-BOCS score 8 or below Remission: Response that reduces symptoms to minimal level; Y-BOCS score 16 or less

15 1) 2) 3) 4) 5) No clear definition Usually those who undergo adequate trials of first-line therapies without achieving a satisfactory response Issues to be considered before defining patient as being treatment resistance: Surety of dx Adequacy of treatment Potential presence of medical/psychiatric co-morbidity Evaluate potential role of family in reinforcing the disorder Partial responders may show full response with continued treatment beyond 3 months

16 Switching to another SSRI Augmentation with psychotherapy Role of clomipramine in OCD treatment: The Expert Consensus Guidelines on the Treatment on OCD, 1997 recommends: Switch to another SSRI after a non-response to a first SSRI Switch to clomipramine only after 2 to 3 failed SSRI trials

17 Tricyclic antidepressant with strong serotonin reuptake inhibitor with weak norepinephrine reuptake blockade Most extensively studied medication in the treatment of OCD Efficacy shown in multiple controlled trials May have small superiority over SSRIs Used as monotherapy or combination with SSRI

18 However, typically not used as first-line Due to side effect profile: Sedation, postural hypotension Anticholinergic side effects: dry mouth, blurred vision, constipation, urinary retention, confusion, diminished working memory Lowers seizure threshold Cardiac toxicity, lethal in overdoses

19 Start at 25 mg at night, increase by 25 mg every 4 days or 50 mg every week Usual target dose mg/day, 150 to 200 mg Usual maximum dose 250 mg The average reduction in OCD symptoms ~ 40% 60% of all patients clinically much improved Improvement may be slow, maximum response seen after 5 to 12 weeks Effective equally for pure obsessions and those with rituals

20 Neurobiological basis: dopaminergic hyperactivation of OCD Second generation antipsychotics: Risperidone, Quetiapine, Olanzapine, Aripiprazole: Combination of antagonism at D2 and 5HT2a receptors Double-blind, placebo-controlled studies support the efficacy of augmenting SRIs with 2nd gen antipsychotics Significant efficacy for Risperidone Possibly Olanzapine, Aripiprazole as well First generation antipsychotic: only Haloperidol proved effective

21 Weak evidence for combination of 2 SSRIs Weak evidence for combining SSRI with other medications: Lithium, Buspirone, Clonazepam, Naltrexone, Lamotrigine, Memantine, Caffeine Switch to Venlafaxine, Duloxetine, Mirtazepine, Agomelatine Preliminary studies positive for venlafaxine (dose at or above 225 mg/day); duloxetine at 120 mg/day

22 Supratherapeutic SSRI doses: May be effective but caution on side effects & adverse reactions eg dose-dependent QTc prolongation with citalopram IV clomipramine: Avoids first-pass metabolism Rapidly achieves high plasma level

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24 Either pharmacotherapy or psychotherapy alone may be chosen as first-line treatment for OCD, depending on patient preferences, values and economic considerations The first-line pharmacological treatment for OCD should be a 10 to 12 week trial with an SSRI at adequate doses Clomipramine may be used as a treatment for OCD after an adequate trial of SSRI treatment has failed Venlafaxine may be considered in patients who have not responded to SSRIs and Clomipramine. Monitor blood pressure during treatment. CBT augmentation of serotonergic antidepressants may be considered for those who are treatment resistant or partially responsive to medications Patients who respond to antidepressants in the acute phase should be continued on their medications for at least 12 months

25 Earlier age of onset Longer duration of illness Poorer social functioning at baseline Have both obsessions and compulsions Magical symptoms Hoarding obsessions and compulsions

26 When diagnosis is not certain?psychosis With other co-morbidities Depression with suicidality Eating disorders Substance use Psychotic disorders Tourette s disorder Failure of response to first-line treatment

27 1) 2) May be considered after several pharmacotherapeutic and psychotherapeutic approaches have not been effective; when significant functional impairment remains Functional neurosurgery Neuromodulation: deep brain stimulation Lesioning procedures: cingulotomy, capsulotomy, subcaudate tractotomy, limbic leucotomy

28 Stimulation electrodes implanted into specific brain regions Continuous electrical high frequency stimulation delivered from an implanted, externally programmable pulse generator Target sites: anterior limb of internal capsule believed to disrupt activity in loop fibers that connect cortex with thalamus Possible surgical adverse effects: asymptomatic cerebral hemorrhage, seizure, superficial wound infection, break in stimulating lead or extension wire Psychiatric adverse effects: transient hypomanic symptoms, worsened depression and OCD when DBS stimulator battery is depleted

29 Performed using stereotactic techniques A method neurosurgeons use to visualize the brain as volume in a 3D space, then referenced to a specific coordinate system Allows precise reaching of subcortical brain structures with minimal disruption of surrounding tissue Used with functional neuroimaging and physiological recordings To modulate interactions between various components of the frontal cortex and cingulate cortex with basal ganglia and thalamus

30 Most common neurosurgical procedure for treatment of refractory psychiatric syndromes; particularly OCD Anterior portion of cingulate gyrus is lesioned Interrupts tracts between cingulate gyrus and frontal lobes Eliminates efferent projections of anterior cingulate cortex

31 Capsulotomy Targets anterior limb of internal capsule Relay route between cortical structures and thalamus Subcaudate tractotomy Targets region of white matter localized beneath head of caudate substantia innominata Interupts relay between cortex and thalamus via striatum Mainly used for treatment of refractory depression Limbic leucotomy Combination of subcaudate tractotomy and cingulotomy

32 Umberto Albert, Andrea Aguglia, Stefano Brumante, Filippo Bogetto, Giuseppe Maina (2013). Treatment-Resistant ObsessiveCompulsive Disorder (OCD): Current Knowledge and Open Questions. Clinical Neuropsychiatry. 10,1,19-30 Sahib Khalsa, Jason Schiffman, Alexander Bystritsky (2011). Treatment-resistant OCD: Options beyond first-line medications. Current Psychiatry. 10,11 Wayne Goodman, Lawrence Price, Steven Rasmussen (1989). The Yale-Brown Obsessive Compulsive Scale. Arch Gen Psychiatry 46: Hales, Yudovsky. Textbook of Clinical Psychiatry (Fourth Edition) Kaplan and Sadock s Synopsis of Psychiatry (Tenth Edition) Jerrold F. Rosenbaum. Handbook of Psychiatric Drug Therapy (Fifth Edition)