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The Case Against Medical Marijuana in Epilepsy The Case Against Medical Marijuana in Epilepsy

The Case Against Medical Marijuana in Epilepsy - PowerPoint Presentation

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The Case Against Medical Marijuana in Epilepsy - PPT Presentation

CLAE 2016 Dr Mark Sadler Dalhousie University Halifax NS Disclosures I have received honoraria from Eisai and UCB Canada I have no disclosures relevant to this presentation Previous Speakers ID: 754787

patients treatment sept epilepsy treatment patients epilepsy sept cannabinoids included reports groups report 2013 gloss vickrey current adverse trial

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Slide1

The Case Against Medical Marijuana in Epilepsy CLAE 2016

Dr. Mark SadlerDalhousie UniversityHalifax, NSSlide2

DisclosuresI have received honoraria from Eisai and UCB Canada

I have no disclosures relevant to this presentationSlide3

Previous SpeakersDr

Richard McLachlanDr Mac BurnhamDr

Jose Tellez-ZentenoSlide4

The Question: Is Marijuana Useful in the Treatment of Epilepsy?Slide5

Is This Really Even of Interest?Google Search: “Epilepsy” and “Marijuana”Slide6

Is This Even of Interest?

Google Search: “Epilepsy” and “Marijuana”Apparently so (to a lot of people)Slide7

How about EVIDENCE from Medical Literature?(Quick search: PubMed Sept 2016: no filters)Slide8

How about EVIDENCE from Medical Literature?

(PubMed Sept 2016)Filter for past

10 years: 237 reduced to 120Slide9

How about EVIDENCE from Medical Literature?

(PubMed Sept 2016)Past 10 years

Filter forPast 5 years

Comment: The recent literature is growing “like a weed”Slide10

How about EVIDENCE from Medical Literature?(PubMed Sept 2016)

X

XSlide11

EBM: Any Systematic Reviews?Slide12

EBM: Any Systematic Reviews?Slide13

Gloss B, Vickrey B: Cannabinoids for Epilepsy.

(Current as of Sept 2013)Objective: To assess the efficacy and safety of cannabinoids when used as monotherapy or add-on treatment for people with epilepsySlide14

Gloss B, Vickrey B: Cannabinoids for Epilepsy.

(Current as of Sept 2013)Objective: To assess the efficacy and safety of cannabinoids when used as monotherapy or add-on treatment for people with epilepsy

Search Methods: Cochrane Epilepsy Group Specialized Register, Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), ISI Web of Knowledge, CINAHL (EBSCOhost), and ClinicalTrials.gov. In addition, included studies authors personally knew about that were not found by the searches, as well as searched the references in the identified studies.Slide15

Gloss B, Vickrey B: Cannabinoids for Epilepsy.

(Current as of Sept 2013)Selection criteria: Randomized controlled trials (RCTs) whether blinded or notSlide16

Gloss B, Vickrey B: Cannabinoids for Epilepsy.

(Current as of Sept 2013)Selection criteria: Randomized controlled trials (RCTs) whether blinded or notData analysis:

Primary outcome: seizure freedom at one year or more, or three times the longest interseizure intervalSecondary outcome: responder rate at six months or more, objective quality of life data, and adverse events.Slide17

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol

as the treatment agent

One report was an abstract; one was a letter to the editor.

Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects

.Slide18

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol (CBD) as the treatment agent

One report was an abstract; one was a letter to the editor.

Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects.Slide19

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol as the treatment agent One report was an abstract; one was a letter to the editor.

Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects

.Slide20

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol as the treatment agent One report was an abstract; one was a letter to the editor. Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects.Slide21

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol as the treatment agent One report was an abstract; one was a letter to the editor. Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects.Slide22

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol as the treatment agent One report was an abstract; one was a letter to the editor. Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects.Slide23

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Current as of Sept 2013)

RESULTS

4 randomized trial reports that included a total of 48 (!!)patients Each used cannabidiol as the treatment agent One report was an abstract; one was a letter to the editor. Details of randomisation were not included in any study report

No investigation of whether the control and treatment participant groups were the same or different.

“All the reports were low quality”

None of the patients in the treatment groups suffered adverse effects.Slide24

Gloss B, Vickrey B: Cannabinoids for Epilepsy. (Up-to-date Sept 2013)

CONCLUSIONS

No reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy. The dose of 200 to 300 mg daily of cannabidiol

was safely administered to small numbers of patients generally for short periods of time, and so the safety of long term

cannabidiol

treatment cannot be reliably assessed.Slide25

The Trial: Lancet Neurology 2016;15:270-78 (online December 23, 2015)Slide26

MethodsDevinsky et al 2016

Multicenter ( N= 11); recruitment over 12 months; US of APatients 1-30 yearsSevere medically resistant epilepsy

Uncontrolled, open label, add on CBD 2-5mg/kg titrated to 25-50 mg/kgPrimary objective: Safety and tolerability of CBDPrimary efficacy endpoint: “Median % change in the mean monthly frequency of motor seizures at 12 weeks”Slide27

Results: Patients:Min 12 weeks F/U

Slide28

PatientsSlide29

Adverse Events (in > 5% of 162 patients):

Somnolence = 25%Decreased appetite = 19%Diarrhoea = 19%Fatigue = 13%Convulsion = 11%Status epilepticus = 8%

A few others…Slide30

Treatment emergent Serious Adverse Effects*(*Investigator reports possibly related to CBD use)

Status epilepticus: 6%Diarrhoea: 2%Several other single instances… Slide31

EfficacyBaseline median monthly f of motor seizures = 30

At 12 weeks = 15.8Median change in monthly motor seizures = - 36.5% 39% of patients had a reduction of 50% or more of motor seizures (5 patients seizure free = 4%) Slide32

Critique and Commentary

Authors’ comments cautious; conservative; acknowledged deficienciesA study of purified “CBD” not “marijuana”No control group;

Unblinded* (see next slide)Short baseline period (4 weeks)About 1/3 of patients had an INCREASE in Sx

f and 1/3 had < 50%

Sx

reduction (Bauer PB, Sander JW Lancet Neurology 2016. Letter to editor).

Effect of CBD on

clobazam

metabolite (N-

desmethyl

clobazam

): Post hoc analysis

70 patients WITH

clobazam

: 51% had >50% reduction in

Sx

f

67 patients NOT taking

clobazam: 27% had > 50% reduction in Sx fSlide33

Importance of Blinding & Placebo: Example(Press CA et al. Epilepsy and Behavior 2015)

Retrospective study of oral cannabis extracts (OCEs) in Rx of pediatric epilepsy in Colorado75 patients of whom 1/3 reported a >50% reduction in Sx

fMajor Result:If parents MOVED to Colorado for OCEs: 47% responder rate vs 22% if already lived in ColoradoSlide34

Return to The Question: Is Marijuana Useful in the Treatment of Epilepsy?

CBD: Worthy of a double blind placebo controlled trial: Sure

√“Marijuana” in various other forms: NO RELIABLE EVIDENCE“Regular marijuana”:Dose?Mode of administration? Smoke: lung function

etc

“Lot-to-lot” variation in concentration?

Adverse effects . See

Volkow

et al NEJM 2016

Therefore: use of “regular” marijuana outside of a clinical trial is…Slide35