Thursday, January 18, 2007

Ritalin or Abilify for I.V. Amphetamine Dependence

Here's an interesting article from Finland in the American Journal of Psychiatry [PubMed] looking at potential treatments for intravenous amphetamine or methamphetamine (speed or ice) dependence.

Since amphetamines are dopamine agonists, the thinking was to replace it with another dopamine agonist (such as methylphenidate/Ritalin) or a partial agonist (such as aripiprazole/Abilify), in much the same was heroin is replaced by methadone or buprenorphine.

"While methadone and buprenorphine have proven
highly effective substitute medications for opioid depen-
dence (3), no pharmacological treatment has been found
thus far for amphetamine dependence (4). Partial dopa-
mine agonists such as aripiprazole are considered to be
promising medications for addiction, since they are sup-
posed to balance and restore normal function of the me-
solimbic dopamine system (5). Observational studies,
nonrandomized trials, and one randomized study without
a placebo arm have suggested that oral dextroamphet-
amine may be used to replace illicit intravenous amphet-
amine use (4), which suggests that oral methylphenidate
(dopamine reuptake inhibitor) might also be used to sub-
stitute for intravenous amphetamine use. On the basis of
this information, we aimed to compare the effectiveness
of aripiprazole, methylphenidate, and placebo in the
treatment of amphetamine dependence using urinalysis
as an objective measure of primary outcome."

What was interesting about this study, and why they stopped it prematurely, was that they discovered that the Abilify increased the amphetamine abuse. At the end of the double-blind, placebo-controlled study (n=53), looking only at positive urine samples to indicate relapse, 79% of the placebo group relapsed, compared with 46% of the methylphenidate group (54mg/day), and 100% of the aripiprazole group (15mg/day).

"Our results indicate that methylphenidate treatment is
associated with a statistically significant reduction in in-
travenous amphetamine use when compared with pla-
cebo, providing the first controlled evidence of an effective
pharmacological treatment for amphetamine depen-
dence. On the contrary, aripiprazole treatment was associ-
ated with a higher proportion of amphetamine-positive
urine samples than placebo.

While aripiprazole (in amphetamine dependence) and
naltrexone (in opioid dependence) may be good treat-
ments in theory, it seems that effective pharmacological
maintenance treatments for intravenous drug depen-
dence are substances that induce at least some euphoria,
such as methadone and buprenorphine in opioid depen-
dence (3), or methylphenidate in amphetamine depen-
dence. Slow-release methylphenidate may be superior to
usual short-acting formulation, since the patient may start
experiencing cravings for amphetamine as soon as the ef-
fect of the substitute drug disappears. It is likely that meth-
ylphenidate should be dispensed mostly on a daily basis
under supervision because of its abuse potential. Ari-
piprazole (15 mg/day) was not effective in this trial (an ab-
stinence facilitation trial), but we cannot draw any conclu-
sions on its potential efficacy in a relapse prevention study
among detoxified patients.

These results show that amphetamine use began to de-
crease substantially as a function of time after 10 weeks of
methylphenidate treatment reaching statistical signifi-
cance at 18 weeks, which indicates that it may take an
even longer period of time than 20 weeks to achieve full
benefit from this treatment."

So, they suggest that, for treatment purposes, Ritalin:amphetamine::Methadone:heroin, and further suggest daily, administered dosing to reduce abuse, perhaps earning weekend take-homes. Hmm, that doesn't sound too promising, except for maybe court-ordered folks who want to stay out of jail.

But the real take-home message, for me, is to consider avoiding Abilify in pts with psychosis who have a history of comorbid amphetamine abuse.

Amphetamine molecule
Amphetamine molecule. Note the phenyl ring on left, Nitrogen on right, and 2 carbons (ethyl) in middle. The squiggly is where a chemical group would be added to change the type of amphetamine compound.

Methylphenidate molecule
Methylphenidate/Ritalin molecule. Note instead of the N-amino group on the right, there is now a pyridine ring (with the N). That makes it less potent.

Norepinephine molecule
Norepinephrine molecule. Note the common phenyl ring on left, N-amino group on right, and 2-carbons (ethyl) in the middle.

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