PROVISIONAL COST-UTILITY ANALYSIS OF

CBD VS ANTIPSYCHOTICS IN TREATING

BIPOLAR DISORDER

G A R Y G I N S B E R G D R P H , M S C ( E C O N )

M I N I S T R Y O F H E A L T H , I S R A E L G A R Y . G I N S B E R G @ M O H . H E A L T H . G O V . I L

G M G I N S B E R G @ G M A I L . C O M

A F T E R S E P T 1 S T 2 0 1 7

Bipolar challenged persons (1% prevalence) who self-medicate with

marijuana, are often unfortunately exposed to high levels of THC

(contra indicated because of elevated psychosis risk). They also

often receive low levels of CBD, which is a potential anti-psychotic

and antidepressant.

In many Western countries, marijuana with very low THC content

(<1%), is not classified as a drug or dangerous substance. It is

freely available OTC from pharmacists and beauty shops.

Because of dangers of tobacco addiction (which causes 8000+

deaths a year in Israel - Ginsberg G. IJHSR 2014) it is

recommended that CBD is taken without tobacco (oil, wax).

Cannabis with high CBD content (n=1877) has been associated with people

having fewer psychotic experiences (Schubart CD. Schizophrenia Research

2011)

A small randomized (n=42) study (Leweke FM. Transl

Psychiatry 2012) has shown that CBD is not inferior to

Amisulpride, in alleviating psychotic symptoms…..

but CBD has a far safer side effect profile (diabetes

etc…)

Amisulpride is one of the two most effective anti-psychotics, being equivalent to

Olanzapine in the prodromal phase (Deas G. Psychiatr Danub 2016) and (not

significantly) better than Olanzapine in treating acute psychosis (Nuss P.

Therapeutics and Clinical Risk Management 2007)).

COST-UTILITY ANALYSIS

Enables us to compare “objectively” different interventions be they

Preventive, curative, palliative, mainstream or alternative.

Ranks interventions in terms of Costs per avoided Disability Adjusted

Life Years (DALYS)

All parameter values are “open for all to see ” and can be subject to

change once new evidence is obtained

Economics Epidemiology

COST - Rx SAVINGS*

Averted DALYs **

* Rx costs using conventional anti-psychotics (OLNZ) less

Rx costs using CBD

* * mortality + morbidity gains

COST-UTILITY RATIO = NET COSTS PER AVERTED DALY

CBD OIL (0% THC)

800 mg per day

$8 per gram

$2,338 per year

OLNZ

5mg per day maintenance

$ 0.79 per day

$263 per year

COSTS (US $ 2017 PRICE LEVELS)

Assumes blood monitoring

costs are same as both groups

will be taking lithium

Assume OLNZ is discontinued and CBD is

introduced 3 months after manic-psychotic episode

in study group.

ANTI-PSYCHOTICS COUNTER-

INTUITIVELY CAN ACTUALLY

INCREASE RELAPSES

But perhaps the worst side effect is that the blocking of the

dopamine path to the brain causes the body's dopamine

receptors to over-compensate and become oversensitive to

stimuli. Wunderlink (JAMA Psychiatry 2013) reported a RCT

where persons (who had first episode psychosis) who were on

Olanzapine for seven years had 3.5 times as many relapses as

persons who were taken off Olanzapine after a year.

A RCT in Spain was halted by the manufacturers (WHO drug trial archives),

supposedly due to problems in recruiting enough bipolar subjects!. Conspiracy

theorists may hypothesize that this was due to results of discontinuing

Olanzapine after 3 months being at least as good as discontinuing Olanzapine

after a year. (PUBLICATION BIAS)

0 50 100 150 200 250 300

Manic

HypoManic

Stable

Mild Depn

Mod Depn

Sev Depn

DURATION (DAYS) BY DISEASE STAGES

A year when there is a relapse

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Manic

HypoManic

Stable

Mild Depn

Mod Depn

Sev Depn

PATIENT DISABILITY WEIGHT BY DISEASE

STAGES

Salamon, Lancet 2012 0.064 DALY

LOSS

0 0.05 0.1 0.15 0.2 0.25

Manic

HypoManic

Stable

Mild Depn

Mod Depn

Sev Depn

CAREGIVER DISABILITY WEIGHT BY DISEASE

STAGES

Just worry in stable phase! 0.033 DALY

A RELAPSE COSTS $ 3,533

50% hospitalization rate at $284 per day for 18 days ($2,559)

Six extra psychiatrist visits at $80 each ($478)

Six extra psychologist visits at $68 each ($407)

Extra cost of acute anti-psychotics (15mg tapering to 5 mg)

($51)

80% experience depression of whom 80% take anti-

depressants ($38)

CBD

0.09 per year

$3,533 per episode

$307 per year

0.006 DALYS

OLNZ

0.22 per year

$ 3,533 per

episode

$762 per year

0.014 DALYS

RELAPSE ESTIMATES

Note: estimates are extremely conservative, actual

rates could be 3-4 times these in both arms

SUICIDES

Conservatively assumed 0.1% of depressive episodes ended in

suicides.

Losing 30 years on average (PYLL), 20 years discounted at 3%.

12.5 discounted HALEs (Healthy adjusted life expectancy)

DALY Loss from Mortality

:CBD (0.001) vs OLNZ (0.003)

CBD

Incidence 0.40% per year

$292 lifetime

costs

0.003 DALY loss

OLNZ

Incidence 1.46% per year

$ 1,066 lifetime costs

0.010 DALY loss

TYPE II DIABETES

Discounted (3%) $73,000 lifetime costs and 0.68

DALY losses per Type II controlled diabetes case

Vancampfort World

Psychiatry 2016. Jaffe Plos

One 2016. Ginsberg IJHPR

2017.

INTERVENTION AND TREATMENT COSTS

OLNZ CBD

$263 $2,338 MEDICATION

$762 $307 RELAPSES

$1,066 $292 DIABETES

$2,092 $2,936 TOTAL

$844 NET COST

DALY LOSSES

OLNZ CBD

0.014 0.006 RELAPSES

0.010 0.003 DIABETES

0.003 0.001 SUICIDES

0.007

0.003 CARER

0.033 0.012 TOTAL

0.021 NET GAIN

ICER = $39,698 =1.01 GNP per capita

BORDERLINE VERY COST EFFECTIVE

COST PER DALY AVOIDED ($) BY CBD COST

-50,000

0

50,000

100,000

150,000

200,000

0 5 10 15 20

CBD cost per gm ($)

COST-

EFFECTIVE

VERY

COST-

EFFECTI

VE

NOT COST

EFFECT

COST-

SAVING

WIN-WIN

CONCLUSIONS

Similar calculations could be made for any THC/CBD mix vs.

conventional pharmaceuticals for any disease.

CBD could well be a cost-effective or even cost-saving alternative to

conventional anti-psychotics in managing bipolar disease.

Main evidence is based on a small study (n=42)

NEED LARGE RCT OF CBD vs anti-

psychotics to manage bipolar

HOW?, WHO WILL FINANCE TRIAL, WHO

WILL PARTICIPATE?

If CBD is proved to be equivalent or superior,

could save hundreds of thousands of people

from side effects of anti-psychotics.