January 2010

Asenapine to Treat Schizophrenia and Bipolar Disorder
The new antipsychotic asenapine (Saphris) appears comparable to other second-generation agents but requires sublingual administration.

Clozapine Plus Other Antipsychotics
A paper by Taylor and Smith suggests that adding another antipsychotic to clozapine (Clozaril and others) for treatment-resistant patients has minimal therapeutic benefit.

Isotretinoin (Accutane) May Exacerbate Symptoms in Patients with Bipolar Disorder
Isotretinoin (Accutane) may destabilize mood in patients with bipolar disorder.

Stimulants Associated with Sudden Death in Young Patients
Stimulants such as methylphenidate may increase the risk of sudden unexplained death in young patients.

In Brief
Depression Risk Lower with 'Whole Foods' Diet; Anxiety during Menopause Not Improved by Black Cohosh

Lithium, Thyroid Function, and Depressive Relapse
Patients with bipolar disorder treated with lithium may develop depressive episodes due to changes in thyroid function.

Fighting Fire with Fire: Injectable Heroin for Heroin Addicts?
Diacetylmorphine merits consideration as a treatment of last resort for heroin addicts who don’t respond to methadone therapy.

Fighting Fire with Fire: Injectable Heroin for Heroin Addicts?

January 2010

An estimated 1 million people in North America are believed to be dependent on opioids, usually heroin. Heroin dependence is often accompanied by fatal overdoses, serious infections—including human immunodeficiency virus (HIV), endocarditis, and hepatitis—social disintegration, violence, and crime. Communities bear the costs of associated medical treatments, public health issues, law enforcement, and criminal justice.

Methadone is the most commonly employed opioid substitution therapy for opiate-dependent patients willing to undergo treatment (BTP 2007;30:29-30). But 15% to 25% of people treated do not respond well to methadone—typically because they continue to use illicit opioids despite methadone or do not stay in treatment.

Diacetylmorphine, the active ingredient in heroin, has been studied in Europe as an adjunctive maintenance treatment and alternative to methadone. Oviedo-Joekes and colleagues conducted an open-label, randomized controlled trial in Canada comparing injectable diacetylmorphine with oral methadone.1

Long-term users of injectable heroin who had not benefited from at least two previous attempts at addiction treatment, including at least one trial of methadone, were assigned at random to receive methadone (N = 111) or diacetylmorphine (N = 115). Patients self-administered the diacetylmorphine injections under supervision and were evaluated over the course of a year.

In an intention-to-treat analysis, the rate of retention in addiction treatment was 87.8% in the diacetylmorphine group versus 54.1% among methadone subjects (P < .001). Illicit drug use or other illegal activity fell 67.0% among diacetylmorphine subjects versus 47.7% in the methadone cohort (P = .004).

The most common serious adverse events associated with diacetylmorphine injections were overdoses and seizures, which occurred in 10 and 6 patients, respectively. There was one fatality in this study, but it was a methadone-treated patient who died from an opioid overdose. All 7 seizures that occurred at the clinic were classified as related to the study medication. Two occurred in a patient with a history of epilepsy; the other 5 occurred in patients who had used cocaine or benzodiazepines before the seizure.

The results of this study are consistent with those from several European studies, all of which suggest that diacetylmorphine is more effective than methadone as a maintenance treatment for long-term treatment-refractory opioid dependence. Some have argued that this approach might allow patients to increase their spending on other illicit drugs, but this has not been observed in research studies. Oviedo-Joekes and her group report an overall reduction in the money spent on illicit drugs in both the diacetylmorphine and methadone groups.

Overdoses and seizures are serious and potentially lethal adverse events associated with diacetylmorphine. In the current study, patients were under close medical supervision, these reactions were promptly treated, and all diacetylmorphine-treated patients recovered. The authors emphasize that because of the serious risk of respiratory depression, injectable heroin, which is less safe than oral opioids, should be delivered only when prompt medical intervention is available.

In an accompanying editorial, Berridge writes that some European countries have made the prescription of heroin legal.2 Voters in Switzerland overwhelmingly passed a referendum in 2008 allowing the continued prescription of heroin. The British National Treatment Agency for Substance Misuse stated in 2003 that IV heroin should be prescribed as a last resort and under the medical control of a specialist. While Switzerland and the Netherlands have integrated the prescription of heroin into their medical systems, Germany and Spain have not.

A recent Cochrane review concluded that maintenance treatment with buprenorphine (Suboxone and others), another substitution therapy for patients addicted to heroin, was significantly less effective than methadone maintenance.3 Oral methadone appears safer than injectable diacetylmorphine, but in a sequenced algorithm for treating opiate dependence, diacetylmorphine merits consideration as a treatment of last resort.

1Oviedo-Joekes E, Brissette S, Marsh DC, Lauzon P, Guh D, Anis A, Schechter MT: Diacetylmorphine versus methadone for the treatment of opioid addiction. N Engl J Med 2009;361:777-786.

2Berridge V: Heroin prescription and history. N Engl J Med 2009;361:820-821.

3Mattick RP, Kimber J, Breen C, Davoli M: Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2008;2:CD002207.