Any news of innovative treatment options in schizoaffective disorder?

Transcription

1 Any news of innovative treatment options in schizoaffective disorder? Andrea Murru, MD, PhD Lisbon, 26th of April 2015 Centro de Investigación Biomédica En Red de Salud Mental

2 Conflitti di Interesse Name speaker Name of Company Product Research grants Others (speaker fees, educational grants, etc.) Andrea Murru Adamed x AstraZeneca Bristol-Myers- Squibb Janssen-Cilag Lundbeck Otsuka x x x x x

3 Scientific production for schizoaffective disorder Treatment plan for schizoaffective disorder Publications (#) Years Schizophrenia Bipolar disorder Murru et al., Psychother Psychosom Confirm the diagnosis 2. Examine predictors of outcome: - Previous functioning - Number of episodes - Persistence of psychotic symptoms - Cognitive impairment 3. Pharmacotherapy: - Rank the evidence - Previous treatments - Ensure tolerability - Treatment adherence 4. Psychological interventions Vieta. J Clin Psychiatry 2010

4 I see schizoaffective patients

5 Evidence on schizoaffective samples Murru et al., Eur Neuropsychopharmacol 2011

6 Evidence-based treatment of schizoaffective disorder Limited specific standalone placebo-controlled trials: Canuso et al (two x paliperidone extended release) Other trials are limited to: Pooled analysis/sub-analysis Including Keck et al (ziprasidone) and Glick et al (aripiprazole) Adjunctive placebo-controlled trials Including Chengappa et al (topiramate) Comparative trials Including Tran et al (olanzapine versus haloperidol) and Janicak et al (risperidone versus haloperidol) Mixed samples (generally schizophrenia and schizoaffective) Practically all antipsychotics Large observational studies Including Vieta et al (risperidone) Indirect evidence Schizophrenia and bipolar trials (all antipsychotics) Murru et al., Eur Neuropsychopharmacol 2011

7 Switching antispychotics in schizoaffective disorder: a systematic review 1412 papers returned by database search: - Clinicaltrials.gov: Cochrane library: 37 - EMBASE: 0 - Pubmed/Medline/Index Medicus: 773 Drug Evidence aripiprazole + lurasidone + risperidone LAI +/- risperidone +/- Evidence from studies: 14 a. 1 study specifically conducted on SAD population b. 13 studies including SAD subsample of appropriate minimum size ziprasidone +/- Murru A et al., World J Biol Psych, 2015

8 Personalized treatment plan Symptoms Symptoms Treat Treat Syndromes Syndromes Vieta, 2010

9 Personalizing the treatment plan Hallucinations 4 Hallucinations 4 Mania 3 Delusions Mania 3 Delusions Depression 0 Disorganized Speech Depression 0 Disorganized Speech Impaired Cognition Abnormal Psychomotor Behavior Impaired Cognition Abnormal Psychomotor Behavior Negative Symptoms Negative Symptoms Hallucinations 4 Hallucinations 4 Mania 3 Delusions Mania 3 Delusions Depression 0 Disorganized Speech Depression 0 Disorganized Speech Impaired Cognition Abnormal Psychomotor Behavior Impaired Cognition Abnormal Psychomotor Behavior Negative Symptoms Negative Symptoms Adapted from DSM-5, APA 2013

10 Polarity Index in maintenance treatment of bipolar disorder and schizoaffective? PI = 1 QUE 1.14 LI 1.39 OLZ 2.98 ZIP 3.91 ARI 4.38 RLAI Predominantly Antidepressive PI Predominantly Antimanic PI LAM 0.40 VPA 0.49 OXC 0.62 Popovic D, et al. Eur Neuropsychopharmacol, 2012

11 Combination therapy: a role for classical mood stabilizers? Schizophrenia Lithium Leucht et al., 2004, Leucht et al.,2007 Valproate Schizoaffective???? Bipolar BALANCE, 2010 Basan et al., 2004; Glick et al., 2009 McElroy et al., 1987; Glick et al., 2009 Hayes, 1989; Bogan, 2000 Fountoulakis et al., 2012 Lamotrigine Glick et al., 2009; Goff et al., 2007?? Glick et al., 2009 Erfurth et al., 1998 Fountoulakis et al., 2012

12 Adherence to oral treatment in bipolar schizoaffective disorder Affective onset and a low number of purely psychotic episodes have been found to positively correlate with treatment adherence. 100 * p=0.035 Percentage of N Poorly adherent Adherent Poorly adherent * Adherent N=76 Affective onset The more affective the clinical course of the illness, the better the adherence to treatment. Murru et al., Acta Psychiatr Scand, 2012

13 Unpredictability in schizoaffective disorder Bipolar Disorder type I Model poor/good adherence partially explained by: Bipolar Schizoaffective Disorder Model poor/good adherence partially explained by: 1. Personality comorbidity (OR 3.0) 2. Total manic recurrences (OR 1.2) Model NOT able to predict good/poor adherence? Murru et al., JAD, 2013

14 Insight improvement in EUFEST study Pijnenborg et al., Eur Neuropsychopharmacol, 2015

15 Compliance: efficacy-aimed strategy? In RCTs, pooled data on LAIs did not reduce relapse compared with oral APs in schizophrenia patients. BUT Kishimoto et al., Schizoph Bull, 2014* Kishimoto et al., J Clin Psychiatry, 2013

16 LAIs in schizoaffective disorder.1 Risperidone LAI Lasser et al., JAD, 2004 Mohl et al., J Psychopharmacol, 2005

17 LAIs in schizoaffective disorder.2 1. Stabilization: PANSS<70, YMRS <12, HDRS < months double blind follow-up patients, 170 PBO and 164 PPAL Fu et al., J Clin Psych 2015

18 Targeting cognitive dimension Citalopram did not differentiate from placebo in cognitive symptom amelioration in a mixed Sch-SZA sample Dawes et al., Neuropsychibiol 2012 Pravastatin did not differentiate from placebo in cognitive symptom amelioration in a mixed Sch-SZA sample Vincenzi et al., Schizoph Res 2014

19 Upcoming and ongoing studies From 1. NCT RCT on methotrexate in mixed Sch+ and SZA sample Chaudry et al., 2015 Trials (protocol) 2. NCT adj treatment RCT with raloxifene, mixed Sch+ and SZA sample 3. NCT aspirin minocycline, pramipexole adj treaatment RCT, mixed Sch+ and SZA sample 4. NCT Retrospective Case Control on TMS+RSP vs. RSP

20 Conclusions May 2015 Poor diagnostic definition Controlled data Role of cyclicity Combination therapies Improved with DSM-5? Still most from mixed data Li + and anticonvulsants? AAPs+MS or AAPs+AD? Attitude towards illness Need to address cognitive impairment! LAIs in first-episode patients? Refractory cases? Clozapine and ECT? CLINICAL GUIDELINES

21 The universe of unmet needs Social functioning Quality of life Job satisfaction Economic needs Deconstructing stigma Family interventions Evidence-based treatments Pharmacogenetics Personalized treatment Etiology Diagnostic stability Side-effects management Biological markers Integrated treatments Psychological interventions Biophysical interventions Illness awareness Treatmentresistant patients Cognitive impairment management Adherence enhancement

22 Thanks! Antoni Benabarre C Mar Bonnín Francesc Colom Mercè Comes Marina Garriga Iria Grande José M. Goikolea Diego Hidalgo Esther Jiménez Anabel Martínez-Arán Andrea Murru Isabella Pacchiarotti Rosa M. Palau Dina Popovic María Reinares Jose Sánchez-Moreno Brisa Solé Carla Torrent Imma Torres Marc Valentí Eduard Vieta