PMID- 36174323
OWN - NLM
STAT- MEDLINE
DCOM- 20221214
LR  - 20221221
IS  - 2211-0356 (Electronic)
IS  - 2211-0348 (Linking)
VI  - 68
DP  - 2022 Dec
TI  - Effects of Sativex(Ⓡ) on cognitive function in patients with multiple sclerosis: 
      A systematic review and meta-analysis.
PG  - 104173
LID - S2211-0348(22)00678-2 [pii]
LID - 10.1016/j.msard.2022.104173 [doi]
AB  - BACKGROUND: Cognitive impairment is a common manifestation of multiple sclerosis 
      (MS). OBJECTIVE: To assess by systematic review and meta-analysis available 
      evidence regarding the impact of nabiximols oromucosal spray on cognition in 
      patients with MS. METHODS: A systematic literature search of clinical studies 
      (all types, any comparator) that measured cognitive function in patients with MS 
      spasticity treated with nabiximols. Meta-analysis for cognitive endpoints was not 
      possible due to heterogenous measurement instruments and outcomes. Meta-analysis 
      was performed for adverse events (AEs) of special interest (cognition disorders) 
      reported in randomized controlled trials (RCTs) of nabiximols versus placebo in 
      patients with MS (with or without spasticity). Certainty of evidence and risk of 
      bias were assessed. RESULTS: Seven clinical studies (three RCTs) directly 
      assessing cognitive function were included in the qualitative analysis. There was 
      no consistent evidence to suggest that nabiximols causes cognitive impairment as 
      assessed by a range of specific psychometric instruments across cognitive 
      domains. Thirteen double-blind, placebo-controlled RCTs (nabiximols, n = 964; 
      placebo, n = 904) were included in the meta-analysis of cognitive AEs. Most 
      cognitive AEs (30 of 32 events, 93.8%) reported with nabiximols in MS patients 
      occurred with not in-label use, i.e., dosage >12 sprays per day and/or not 
      administered primarily for treatment of spasticity. CONCLUSIONS: Within the 
      limitations of the review, we can conclude that no detrimental effects of 
      nabiximols on cognitive function were observed in patients with MS spasticity 
      during up to 12 months follow-up and that cognitive AEs were rare and occurred 
      only when nabiximols was not used according to its approved label.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Dykukha, Igor
AU  - Dykukha I
AD  - Medical Affairs, Almirall Hermal GmbH, Reinbek, Germany.
FAU - Essner, Ute
AU  - Essner U
AD  - O. Meany Consultancy GmbH, Hamburg, Germany.
FAU - Schreiber, Herbert
AU  - Schreiber H
AD  - Neurological Practice Center, Neuropoint Academy, NTD & Neurosys, Ulm, Germany.
FAU - Raithel, Lina Marie
AU  - Raithel LM
AD  - COGITO Center for Applied Neurocognition and Neuropsychological Research, 
      Dusseldorf, Germany.
FAU - Penner, Iris-Katharina
AU  - Penner IK
AD  - Department of Neurology, Medical Faculty, Heinrich Heine University, Dusseldorf, 
      Germany. Electronic address: Iris-Katharina.Penner@uni-duesseldorf.de.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20220914
PL  - Netherlands
TA  - Mult Scler Relat Disord
JT  - Multiple sclerosis and related disorders
JID - 101580247
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 7J8897W37S (Dronabinol)
RN  - 0 (Drug Combinations)
SB  - IM
MH  - Humans
MH  - Treatment Outcome
MH  - *Cannabidiol/adverse effects
MH  - Dronabinol/therapeutic use
MH  - Muscle Spasticity/drug therapy/etiology
MH  - *Multiple Sclerosis/complications/drug therapy/chemically induced
MH  - Drug Combinations
MH  - Cognition
MH  - Double-Blind Method
MH  - Randomized Controlled Trials as Topic
OTO - NOTNLM
OT  - Cognitive function
OT  - Meta-analysis
OT  - Multiple sclerosis
OT  - Nabiximols
OT  - Spasticity
OT  - Systematic review
COIS- Declaration of Competing Interest Igor Dykukha is an employee of Almirall Hermal 
      GmbH and serves as medical advisor. Ute Essner has received honoraria for 
      consultancy services from Almirall Hermal GmbH and Granzer Regulatory Consulting 
      & Service. Herbert Schreiber has received honoraria and personal compensation for 
      serving as a speaker at scientific meetings and member of advisory boards from 
      Almirall, Alnylam, Bayer Pharma, Biogen, Merck, Novartis, Roche and Teva. He has 
      received research grants from Bayer, Biogen, Novartis and Teva. Lina Marie 
      Raithel has nothing to disclose. Iris-Katharina Penner has received honoraria for 
      speaking at scientific meetings, serving at scientific advisory boards and 
      consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, 
      Celgene, Desitin, Sanofi-Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She 
      has received research support from the German MS Society, Celgene, Novartis, 
      Roche, and Teva. Almirall is a partner of GW Pharmaceuticals (developer of 
      Sativex) in Europe.
EDAT- 2022/09/30 06:00
MHDA- 2022/12/15 06:00
CRDT- 2022/09/29 18:18
PHST- 2022/01/05 00:00 [received]
PHST- 2022/09/05 00:00 [revised]
PHST- 2022/09/08 00:00 [accepted]
PHST- 2022/09/30 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/09/29 18:18 [entrez]
AID - S2211-0348(22)00678-2 [pii]
AID - 10.1016/j.msard.2022.104173 [doi]
PST - ppublish
SO  - Mult Scler Relat Disord. 2022 Dec;68:104173. doi: 10.1016/j.msard.2022.104173. 
      Epub 2022 Sep 14.