New treatments on the pharmacotherapeutic horizon
Amphetamines and cocaine are the most widely used
stimulants in the United Kingdom. "We have little to offer stimulant users
in terms of pharmacotherapy," said Dr JOHN MERRILL, consultant in drug
dependence, Drugs North West, Manchester. However, there are potential
treatments in development that could prove useful.
Cocaine and amphetamines cause an increase in the
neurotransmitters dopamine, noradrenaline and 5HT. The "crash" following
stimulant use causes levels of these neurotransmitters to fall below normal
resulting in depressive symptoms.
Agonists increase levels of dopamine and aim to
minimise the come-down experienced in drug withdrawal. Examples included
amantadine and bromocriptine (which has little effect), and phentermine
and methylphenidate (which also has little effect, except for methylphenidate
when used in people who had attention deficit disorder as children). The
other agonist that has been tried is dexamphetamine. It is the "methadone
for stimulant addiction". Dr Merrill said that 60 per cent of specialists
thought that dexamphetamine substitution therapy had a role in treating
amphetamine addiction. It could also be useful in cocaine addiction.
In terms of antagonists, which are used to block
the action of the stimulant, haloperidol and flupentixol had been tried
but did not work. Trials are ongoing on the efficacy of newer antipsychotics
such as clozapine, olanzapine and risperidone.
Antidepressants, including imipramine, selective
serotonin reuptake inhibitors, venlafaxine and reboxetine have been tried
and all took several weeks to have any effect which is problematic for
withdrawal. Monoamine oxidase inhibitors have also been tried. They work
in a similar way to disulfiram in alcohol addiction. However, the effect
of MAOIs and cocaine taken together are severe.
The future of treatment might lie with peripheral
cocaine blocking agents (PCBAs), such as butyrylcholinesterase, and cocaine
vaccines, Dr Merrill said. Butyrylcholinesterase is an enzyme that metabolises
cocaine in the body, and a long-lasting injection of this could be used
to block the action of cocaine before it reached the brain. Two questions
remained over its use: could it act fast enough (and metabolise the cocaine
before the cocaine reached the brain) and would other pathways of cocaine
metabolism be altered as a result of giving butyrylcholinesterase?
Cocaine "vaccines" are also in development which
may be able to give immunity from the effects of cocaine for up to seven
months.
"There are enormous potential ethical issues surrounding
use of these vaccines, including which populations should be vaccinated
and the fact that blood tests would be able to detect if someone had been
given the vaccine," he said.
Opiates
New drugs on the market and increased evidence on
the way to use older treatments safely mean that there have been significant
advances in treating opiate addiction in the past 10 years, said Dr EMILY
FINCH, consultant psychiatrist, Maudsley Hospital, London.
Methadone is still the most effective treatment
for opiate addiction and it will probably remain the mainstay for the
time being. There is now an increased awareness of the need for safer
management of methadone such as daily dispensing and supervised dispensing
in pharmacies, if possible, she said.
A new drug for treating opiate addiction is buprenorphine.
It has been used widely in France where it is the most commonly used drug
for opiate substitution. In the UK, it is used more for withdrawal. It
can be dispensed daily and be supervised too, if the service is available.
Trials indicate that buprenorphine is as effective as 40ml methadone but
less effective than 80ml daily. Buprenorphine has a lower death rate on
therapy than methadone, said Dr Finch. This is because of its partial
agonist effect making it is less likely to cause respiratory depression
than methadone.
Lofexidine is the most widely used drug for detoxification
and causes fewer problems with postural hypotension than clonidine. Following
detoxification, the opioid receptor blocker naltrexone can be taken for
maintaining abstinence and is effective in more compliant patients. Ultra-rapid
detoxification with naltrexone, clonidine or lofexidine, and anaesthesia,
is feasible but can lead to death.
There is continued interest in the use of diamorphine
to treat addiction and between 200 and 300 people in the UK are prescribed
it, she said. In Switzerland, supervised injecting of diamorphine three
times a day is used but more work is needed to assess its use, she said.
Alcohol
An efective treatment for alcohol addiction does
not yet exist, although many agents have been tried. The ideal agent would
be effective against all the symptoms of detoxification, be an anticonvulsant
and prevent delirium, have a rapid onset of action, have no interaction
with alcohol and no potential for abuse, said Dr CHRIS DALY, consultant,
Drugs and Alcohol North West, Manchester.
Benzodiazepines, eg, chlordiazepoxide, are the first-line
treatment for detoxification. Clomethiazole is not used much now because
of its major interaction with alcohol and potential for abuse. Alpha2
agonists and beta-blockers are effective at controlling some symptoms
of withdrawal but do not have any anticonvulsant action. Anticonvulsants
themselves, particularly carbamazepine, are used as second-line treatments
in detoxification.
Naltrexone is awaiting a licence for treating alcohol
addiction in the UK, he said. Patients in trials taking naltrexone are
more likely to be able to return to normal drinking, or abstinence, than
those on placebo and they report less of a high from drinking. He explained
that the reason why naltrexone worked is because one of alcohol's actions
is a positive reward effect on endogenous opiate receptors. Naltrexone
augments the sedatitive effect and lowers the stimulative effect of alcohol,
he added. Its role in controlling drinking rather than in abstinence is
being looked at now.
Among patients given disulfiram, most test it out
to see whether or not they have a response. So in effect the drug reduce
the quantity of drinking but does not achieve total abstinence. In terms
of antidepressants, SSRIs should be avoided in patients with early onset
familial alcoholism because they will make the symptoms worse rather than
better.
Alcoholics are prone to thiamine deficiency because
of poor diet and the effect of alcohol on thiamine absorption in the gut,
so vitamin supplementation is important, he said. "Vitamin prophylaxis
is very important and underused." For people with symptoms of vitamin
B deficiency, including alcohol psychosis, and those considered to be
at risk of it, intravenous supplementation should be given. For those
at lower risk, thiamine 50mg four times a day could be given.
Nicotine
Specialist smoking cessation clinics had been a
real success, said Professor ROBERT WEST, department of psychology, St
George's Hospital medical school, London. However, the funding for them
runs out next April and there has been no word about future funding, he
said.
Some primary care organisations are continuing to
support smoking cessation clinics despite the lack of funding. In addition,
general practitioners vary in their attitude to treatment of nicotine
dependence so it is likely that this will become another area of the NHS
postcode lottery, he added.
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