Neuropsychiatric Disorders in MS N europsychiatric Disorders in - PowerPoint PPT Presentation

Neuropsychiatric Disorders in MS N europsychiatric Disorders in Multiple Sclerosis: Assessment and Management  Adjustment Disorder  Somatic Symptom Disorder  Mood / Affect Disorders:  Psychosis CMSC Annual Meeting 2016 ~ National Harbor, Maryland  Substance- Related Disorders • Major Depression • Bipolar Disorder  Comorbid syndromes & • Other Mood Syndromes disorders: • Pathological Laughing and Laura Safar, MD • Crying (PLC) Fatigue Brigham and Women’s Hospital • • Apathy; disinhibition Sleep Disorders Neuropsychiatry Division  Anxiety Disorders • Pain Center for Brain/Mind Medicine  Cognitive Disorders Psychiatric Disorders in MS: Neuropsychiatric disorders in MS General Considerations Pathophysiology  Primary psychiatric illness  Highly prevalent  Secondary to MS (inflammatory/ autoimmune, brain  Impact on QOL, adherence to DMTs, prognosis lesions)  They may be the initial clinical presentation  2dary to medications  2dary to MS symptoms (fatigue, pain, sleep disorders)  They may signal a relapse  Psychosocial factors (stress/support, coping style)  All of the above combined and interacting

General Approach: Analyze complexity Anxiety  Screen, evaluate, & treat  Screen/evaluate: Sleep Cognitive Dysfunction  PHQ-9: Depression (BDI, HADS) Problems Ms. B: Depression  GAD-7: Anxiety since 20s, +FH.  CNS-LS: PBA Sx worsened  MDQ: Bipolar Disorder since MS  MFIS: Fatigue: Physical, cognitive, social MS physical onset. Isolation, sx: Pain,  Audit-C: Alcohol, substances hypoactivity fatigue  MoCA: Cognitive performance Baclofen,  ADLs and IADLs tizanidine,  Risk: Meds, suicide, falls, abuse, driving, fire, financial. BZD, steroids …and also evaluate: DMTs- possible side effects  Associated MS symptoms (fatigue, pain) Brand name Psychiatric Side effects / other notes DMT  Medical comorbidities (OSA, DM) Interferon beta IM, Avonex (IM), Depression 1a SC  DMTs: Therapeutic & side effects Rebif (SC) SC Interferon beta Betaseron, Depression  Symptomatic treatments including CAMs 1b Extavia Glatiramer SC Copaxone Anxiety  Coping style, values & priorities, motivations IV Natalizumab Tysabri Depression PO Fingolimod Gilenya Neutral or ?Benefit for depression  Support system, stressors, access to treatment, (Montalban- Mult Scler 2011). Monitor QTc treatment team

Symptomatic treatments in MS Treatment: Bring it all back together  Bowel and Bladder  Steroids (depression, agitation, euphoria, insomnia, psychosis)  Oxybutynin  Bio-psycho-social  Neurologist / neurological team  Tolterodine  Pain Treatment   Amitriptyline  Individualized: Mental Heath team (Psychiatrist,  Phenytoin nurse practitioner, Social Worker/  Darifenacin  Carbamazepine Preferences & values psychotherapist,  Trospium  Amitriptyline or Nortriptyline Neuropsychologist)  Longitudinal: Needs  Gabapentin   Fatigue Case manager vary: Educate, anticipate,  Pregabalin  Amantadine  accompany, assist with OT, PT, CRT  Duloxetine  Stimulants planning  Opioids  PCP, Pain specialist, sleep  Modafinil specialist, urologist, other.  Support higher  Dalfampridine ( Ampyra )  Spasticity  Patient and caregivers functioning, positive  Baclofen  Psychotropics/ sleep agents coping skills   Diazepam MS society, community resources,  CAMs web  Dantrolene  Interdisciplinary  Cannabinoids   Tizanidine Attorney (disability/ labor, estate planning)  Intrathecal Baclofen Neuropsychiatric Disorders in MS Mood Disorders in MS Study  Fifty (50) patients with MS seen for treatment in  Adjustment Disorder  Somatic Symptom Disorder outpatient neuropsychiatry clinic.  Mood / Affect Disorders:  Psychosis  Examined on the Patient Health Questionnaire-9 (PHQ-  Substance- Related Disorders • Major Depression 9), the Generalized Anxiety Disorder 7-item scale (GAD- 7), the Center for Neurologic Study-Lability Scale (CNS- • Bipolar Disorder LS) for pseudobulbar affect (PBA), the Mood Disorder  Comorbid syndromes & • Other Mood Syndromes Questionnaire (MDQ), and the Modified Fatigue Impact disorders: Scale (MIFS). • Pathological Laughing and • Crying (PLC) Fatigue  Also evaluated clinically, in initial psychiatric visits lasting • Apathy; disinhibition • Sleep Disorders 75 min and follow up visits lasting 45-60min.  Anxiety Disorders • Pain  Findings from both, clinical evaluation and instruments were analyzed.  Cognitive Disorders

Results Results  MFIS and Depression: Strong correlation between MFIS  PHQ-9 analysis: 66% of our patients had a PMR/SAD scores (total, and sub-scales) and Depression ratio =/> 1.  MDQ and Bipolar Disorder:  PMR= Fatigue, sleep, concentration, psychomotor retardation items  62% of individuals endorsed 1-3 items on the MDQ. This included “non-relevant” responses (eg, distractibility due to  SAD= Decreased interest, sadness, negative self- cognitive dysfunction). thoughts, suicidal thoughts  10 patients endorsed 4 or more MDQ items. Of these, 6 were assessed as presenting bipolar spectrum symptoms.  11 subjects had PHQ-9 Score >5 but not depression. CNS-LS Questionnaire and PBA:  8 subjects had PHQ-9 >10 but mild depression.  9 individuals had scores >13 (suggestive of PBA; highly  Positive correlation between PHQ-9 scores and clinical sensitive but less specific). 3 of those were considered to have mild PBA symptoms, in the context of clinical depression. depression Depression Conclusions  Prevalence:30-50% (Major Depression)  Mood and affect symptoms in MS may include sub-  Clinical Presentation: Similar to primary depression syndromal depression, anxiety, bipolar, and PBA symptoms, as well as the full-fledged disorders.  Comorbid MS symptoms: Fatigue, sleep disturbances, cognitive deficits, PMR  Patients frequently present combined presentations.  Comorbid psychiatric symptoms:  Screening tools may help identify relevant symptoms  Irritability, disinhibition, mood lability efficiently  PLC (Pseudobulbar affect)  Clinical correlation is needed to reach an accurate  Apathy: Syndrome of decreased motivation/ interest diagnosis and select appropriate treatment.  Anxiety

Depression: Treatment Bipolar Disorder  Antidepressants:  Small RCTs: Desipramine (marginal); Sertraline  Open-label trials: Duloxetine; Moclobemide; Fluoxetine; Sertraline;  Prevalence: Twice as common in MS as in the GP Imipramine; Tranylcypromine  Steroids, baclofen, stimulants, may contribute  ECT: Severe, TRD  rTMS, tDCS: Small trials- more research needed  Treatment: Mood stabilizers & atypical antipsychotics  Exercise: Possible reduction in depressive symptoms  Steroids- induced mania: Prophylaxis with mood stabilizers or atypical antipsychotics  Psychotherapy: CBT, MBT, ACT, Positive Psychology  Sub-syndromal “bipolar” symptoms: Irritability, emotional  Treat associated symptoms: Fatigue, cognition, other mood symptoms lability, agitation, disinhibition:  Treat MS (this may need to go to top)  Treat MS symptoms, treat comorbidities Cognitive Disorder Anxiety Disorders in MS  40-70% of individuals with MS exhibit cognitive dysfunction  Prevalence 15-55 %  Clinical presentation:  Common complaints: Difficulty multitasking; organizing; things take  GAD longer to do; increased effort for same tasks; less sharp  Adjustment: Post- diagnosis &  Somatic complaints; relapses  Abilities most commonly affected: differential with MS physical  Unpredictability- MS course, symptoms  Information Processing Speed disability  PD  Memory: Encoding & retrieval  Attention  OCD  It increases suicide risk  Executive function  Treatment: Meds and  Increased use of  Word retrieval benzodiazepines, other psychotherapy as in sedatives, alcohol, cannabis  Deficits may occur early, before physical disability; profile broadens primary anxiety disorders with MS progression; 10-25% of patients develop dementia  Stress-management, ACT,  Office screening: MoCA - Dagenais Can J Neurol Sci 2013 mindfulness  Neuropsychological testing

Cognitive Disorders: Treatment Thank you  Treat depression, anxiety, insomnia, fatigue  Treat MS: DMTs may improve cognition  Reduce polypharmacy  Amphetamine; methylphenidate: May improve attention; processing speed; learning &memory- Benedict 2008; Morrow 2013 & 2009  Modafinil may improve attention- Lange J Neurol 2009  AChEI: Donepezil: Possible benefit. Rivastigmine: Small studies; from none to marginal benefit  Memantine: No benefit; possible neurological worsening (Lovera)(Villoslada 2009) Brigham and Women’s Hospital  Amantadine/pemoline: Small trial; no significantly different from placebo Neuropsychiatry Division  Cognitive Rehabilitation Center for Brain/ Mind Medicine Partners MS Center