The possibility of introducing prescribing options for New Zealand psychologists is currently being considered. Clinicians have been invited to offer opinions on the advisability of such a move and to make suggestions on additional training requirements. Certainly, an extensive understanding of the possible side effects of such medications likely to be prescribed would be required.
In fact, an understanding of the possible short- and long-term side effects of medications in general is already an area that warrants considerably more attention from all those working in mental health. The possible, very serious mental health consequences of ingesting certain prescription medicines are currently outlined in a number of medication inserts. In addition, agencies such as the US Food and Drug Administration (FDA) have published warnings cautioning against the use of some prescription medicines, which they state may cause serious psychiatric disturbance. There are also currently proposals in Britain to give every new drug licensed a ‘suicide rating’.
This reform, based on a system adopted recently in the United States, has been fuelled by a growing body of evidence that drugs that affect the brain can heavily influence behaviour through seemingly innocuous changes in body chemistry. Medicines to treat acne, swelling, heartburn, pain, obesity, high blood pressure and cholesterol, bacterial infections, smoking and insomnia have all been associated recently with psychiatric problems. (Mostrous, 2008).
One such medication is isotretinoin (also known as Accutane or Roaccutane), prescribed for the treatment of acne. This vitamin A derivative, manufactured by Hoffman-La Roche, is one of that company’s most popular and controversial medications. In its most recent warnings the FDA (FDA, 2005), stated:
FDA ALERT [7/2005]: Suicidal Thoughts or Actions: In addition to the strengthened risk management program, FDA continues to assess reports of suicide or suicide attempts associated with the use of isotretinoin. All patients treated with isotretinoin should be observed closely for symptoms of depression or suicidal thoughts, such as sad mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down, or trouble concentrating, or for mood disturbance, psychosis, or aggression. Patients should stop isotretinoin and they or their caregiver should contact their healthcare professional right away if the patient has any of the previously mentioned symptoms. Discontinuation of treatment may be insufficient and further evaluation may be necessary.
The ‘Patient Information Sheet’ for this medication also reads:
Serious mental health problems: Isotretinoin may cause:
- Depression
- Psychosis (seeing or hearing things that are not real)
- Suicidal thoughts or actions
-Aggressive and violent behavior
Although approved for the treatment of “the most severe form of acne (nodular acne) that cannot be cleared up by any other acne treatments” (FDA, 2005), isotretinoin has been used increasingly for the treatment of more mild and moderate forms of acne. “In 1995, doctors calculated that only sixteen percent of prescriptions were for severe disease” (Girling, 2002). As a consequence, it is now estimated that many millions have been treated with isotretinoin worldwide. Unfortunately, the numbers of those who have reported suffering serious mental health side effects has also continued to grow. A research documentary, which screened in November 2006, quoted over 6000 reported cases of psychiatric consequences of isotretinoin use, with “US Health Authorities” estimating this was around one percent of those actually affected (Tinari, 2006). Consistent with this claim, Carleton, Smith, Gelin, and Heathcote (2007) identified ADRs (adverse drug reactions) as an important cause of childhood morbidity and mortality and stated that as many as 95% of ADRs are not reported. In a New Zealand survey of secondary school students (Purvis, Robinson, & Watson, 2004), 14.1% reported having problem acne. It has been estimated that 5000 young New Zealanders take isotretinoin (Lawrence, 2006). By 2006, the Centre for Adverse Reactions Monitoring (CARM) had received 93 notifications of adverse reactions to this medication (MARC, 2006). If US Health Authority estimates are correct (Tinari & Häner, 2006), then around 930 New Zealanders have been significantly affected.
Isotretinoin was introduced on the market, as a treatment for acne, in 1982. By 1983 Hazen, Carney, and Walker had already published details of 24 cases of depression related to its use. These findings reinforced those reported earlier by Myskens (1982), who had been using isotretinoin as a treatment for patients with advanced cancer. Around 25 percent of those patients suffered “psychological changes”. These included 18 cases of depression. Four patients had attempted suicide. Subsequent years have witnessed much debate over the strength of the causal link between isotretinoin and mental health problems. The media have feasted on this debate and the medication “has made the kind of headlines normally reserved for mass murderers or airline disasters” (Girling, 2002). In 2007, Carleton et al. conducted a retrospective analysis of 1193 suspected ADRs in Canadian children (including 58.6% adolescents). The drug most cited was isotretinoin and the most frequent reaction descriptor was psychiatric disorders. In his overview of existing research linking isotretinoin to depression, psychosis, and suicide, O’Donnell (2003), having discussed the well-known birth defects caused by ingestion of isotretinoin during pregnancy, also concluded:
Less well known is the risk of this lipid-soluble chemical to affect the central nervous system. Reports of intracranial hypertension, depression and suicide ideation with accutane use, have prompted an examination of its serious life threatening potential…the public must be informed of the proper limited indication for its use, because depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.
Contrary to this conclusion, however, were the findings of Cohen, Adams, and Patten (2007), who used depression scales to assess signs of mental health disturbance at baseline and after two months of isotreinoin treatment. They found no correlation between isotretinoin use and the development of depression on their measures. This study has subsequently faced criticism since “most complaints about depression (following isotretinoin) come about four months after treatment begins” (“Study”, 2005). However, researcher Siegfried (who had made this comment) and her colleagues (Chia, Lane, Chibnall, Allen, & Siegfried, 2005) assessing levels of depression four months into isotretinoin treatment, also found that signs of this disorder were no more prevalent in these patients than in the conservative therapy group. Both studies measured depression using either the Centre for Epidemiological Studies Depression Scale (CES-D) or the Zung Self-Rating Depression Scale. Finally, consistent with both of these findings, Bremner et al. (2005) reported that, amongst their sample, there were no significant increases in depression scores (Hamilton Depression Scale) following four months of Isotretinoin treatment. However, the Bremner study is much better renowned for the other discoveries made during this research. In a world first, Bremner measured brain functioning in his subjects using [18F]fluorodeoxyglucose positron emission tomography, before and after four months of treatment with either isotretinoin or an antibiotic. Results showed clearly that the isotretinoin treatment, but not the antibiotic treatment, was associated with decreased brain metabolism in the orbitofrontal cortex (–21% change versus 2% change for antibiotic). This is a brain area known to mediate symptoms of depression. It seems that these observable brain function changes may produce symptoms (e.g. anger, aggression, paranoia) not well measured when depression screening tools are used in isolation. Depression scales “cannot take the place of a comprehensive clinical interview for confirming a diagnosis of depression” (WHO, 2008).
