Pharmacology

To the Editor:We thank Tong and colleagues1 for their report on a patient with schizophrenia and clozapine-induced maculopathy, and for highlighting this under-recognised condition. Both typical2 and atypical3 antipsychotic drugs have been reported to cause widespread retinopathy; more recently, there have been reports of rare cases of retinal damage localised to the macula (maculopathy) due to both typical4 and atypical1,5 antipsychotics. The classical hypothesis for widespread pigmentary retinopathy is that drugs are absorbed by melanin in the retinal pigment epithelium (RPE) and act as photosensitisers to damage the RPE. This results in loss of RPE support functions of overlying photoreceptors, which secondarily degenerate. An alternative hypothesis,2 supported by histological and animal studies, is that the problem begins in photoreceptors, with drug-induced blockade of retinal dopamine receptors followed by photoreceptor and subsequent RPE cell loss. Neuroleptic retinal drug toxicity typically involves pigment disruption in the RPE, but the dopamine hypothesis allows for broader combinations of RPE and/or photoreceptor damage. The reasons for the development of maculopathy in some patients, rather than a widespread retinopathy, are not known. This phenomenon is seen in other ocular drug toxicities, particularly hydroxychloroquine. Most drug-induced retinal toxicities are bilateral and symmetrical; asymmetrical cases have rarely been reported. The patient reported by Tong and colleagues is atypical with apparently unilateral macular changes.1 Significant differential diagnoses for unilateral macular pigment and photoreceptor changes include age-related and secondary to retinal conditions, such as central serous chorioretinopathy, inflammatory retinopathies and trauma. Maculopathy limited to the outer neuroretina may occur with the use of other drugs (eg, poppers maculopathy).6 Also, schizophrenia is known to cause illness-related retinal changes in the neuroretina but not in the RPE.7 We agree that patients taking psychotropic medications benefit from a multidisciplinary approach when ocular symptoms and signs develop.

Heather G Mack · RC Andrew Symons

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Jessica Y Tong · Amy Pai · Stephanie H Young

To the Editor: In Adelaide, which comprises 78% of the population of South Australia, municipal wastewater has been subject to bimonthly analysis since 2009 to measure trends in substance use. Beginning in October 2015, there was a precipitous decrease in the detection of oxycodone residues in wastewater samples (Box). This decrease was counter to the long term trend of increasing amounts of this opioid in previous samples. Prescribing data show a continuing increase in the use of prescription opioid analgesics (POAs), including oxycodone, nationally and in SA, during the period between 1992 and 2011.1 There is a strong relationship between the amount of POAs used in a community and the amount of harm from opioid dependence and overdose.1 The cause of this regional trend change in oxycodone use has not been established. On 1 July 2015, there were some significant changes in the regulation of work injuries in SA which led to a decrease in the number of complex long term claimants, and there was also a similar change in South Australian motor vehicle injury regulation in July 2013. Complex injury claims are strongly correlated with POA use;2 however, the role of these factors is highly speculative and there may be many other factors that contributed to the results. The methods used for the bimonthly wastewater analysis in Adelaide have been published before,3 and another group used this process to report changes in population methamphetamine use in Queensland.4 From October 2015, there was a change in the established temporal trend for oxycodone residues detected in Adelaide wastewater (Box). However, over the same period, there is no such trend change for national Pharmaceutical Benefits Scheme (PBS) and Repatriation PBS data for the number of oxycodone prescriptions dispensed (not total doses),5 or for Adelaide wastewater residues of methadone, which is predominantly dispensed for treatment of severe opioid use disorders via a specific program. A limitation of our investigations was that no regional oxycodone prescription or wastewater data from other jurisdictions were available for comparison. Nonetheless, our findings suggest that wastewater analysis could potentially be used to rapidly monitor changes in substance use on a regional basis. Box – Oxycodone and methadone residue in Adelaide wastewater compared with national data for the total number of oxycodone prescriptions supplied, December 2011 – February 20175 PBS = Pharmaceutical Benefits Scheme. RPBS = Repatriation Pharmaceutical Benefits Scheme.

Philip Crowley · Jason M White · Benjamin J Tscharke · Cobus Gerber

To the Editor: Since 1 October 2016, under changes in the Medicines Australia code of conduct,1 the names of all doctors receiving payments from pharmaceutical companies are being published online, together with the dollar amount received; the data will remain available for 3 years. Up until now, this information could only be published with the doctor’s consent. This change — part of the latest edition of the code of conduct — is the industry’s response to attempt to legislate for greater transparency. It represents a significant step forward in the transparency of the relationships between doctors and pharmaceutical companies. In 2015, pharmaceutical company-funded educational expenses for doctors included a $70 000 trip to Sweden for six oncologists and a $176 000 trip to Vancouver for nine dermatologists.2 With the new changes, it is likely that doctors will think twice before accepting large pharmaceutical company funding for educational events, given this information will be available to the public. Despite a considerable body of evidence showing that receipt of meals and sponsorship is associated with altered prescribing patterns,3,4 many doctors continue to incorrectly believe that they can effectively manage the influence of pharmaceutical company promotion on their decision making.4 The challenge for the profession is to foster doctor–pharmaceutical company relationships that benefit patients, while maintaining freedom from undue influence on prescribing habits. This requires system and individual change. Medicines Australia should be commended for its efforts to improve transparency; its measures are a lesson for other companies with financial interests relating to the practice and preferences of doctors, including medical devices companies. However, to fully realise the benefit of the code of conduct changes, all information on doctor payments must be accessible via a centralised repository that allows patients and third parties to search for an individual doctor. Regarding individual change, doctors must take heed of the evidence above and eschew gifts and education funding provided by pharmaceutical companies. Moreover, up to date and freely accessible evidence-based information is available via independent organisations such as NPS MedicineWise. Greater transparency in the relationships between doctors and pharmaceutical companies is a positive step to maintaining high levels of accountability and public trust in the medical profession.

Jessica Dean · Malcolm P Forbes · Richard Di Natale

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Anthony Rodgers · Clara K Chow · Rodney T Jackson · Anushka Patel · Tim Usherwood

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Betty SH Chan · Nicholas A Buckley

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Rose Cairns · Jared A Brown · Nicholas A Buckley

In reply

Jennifer H Martin · Yvonne Bonomo