East Asian Arch Psychiatry 2012;22:154-9

ORIGINAL ARTICLE

香港叁间药物滥用诊所的咳药水滥用患者其临床特徵：回顾研究

邓嘉林、邓伟光、梁华君、陈虎、麦舜芝、翁礼和

Dr Alan K. Tang, MBBS, FHKAM (Psychiatry), Department of Psychiatry, Prince of Wales Hospital, Hong Kong SAR, China.
Prof. Wai-Kwong Tang, MBChB, MD, FHKAM (Psychiatry), Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Dr Huajun Liang, MPhil, Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Dr Fu Chan, FHKAM (Psychiatry), Department of Psychiatry, North District Hospital, Hong Kong SAR, China.
Dr Shun-Chi Mak, Department of Psychiatry, Prince of Wales Hospital, Hong Kong SAR, China.
Prof. Gabor Sandor Ungvari, PhD, FRANZCP, FRCPsych, School of Psychiatry & Clinical Neuroscience, University of Western Australia, Perth, Australia.

Address for correspondence: Prof. Wai-Kwong Tang, Department of Psychiatry, 7th Floor, Shatin Hospital, 33 A Kung Kok Street, Ma On Shan, New Territories, Hong Kong SAR, China.
Tel: (852) 2636 7754; Email: tangwk@cuhk.edu.hk

Submitted: 11 June 2012; Accepted: 30 July 2012

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Introduction

In the US, up to 4.9% of 12th graders reported lifetime misuse of cough medicine, with 3.7% reporting misuse within the previous 12 months.¹ In the 2008/2009 survey of drug use among students conducted by the Narcotics Division in Hong Kong, 2.6% of secondary school students reported any type of illicit drugs misuse within the previous 12 months, of which 26.4% was cough medicine.² The first reports of cough mixture abuse surfaced in Hong Kong in the 1980s and, by 2011, 4.4% of male substance abusers reported use of cough mixture, as opposed to only 1.8% of female substance abusers.³ Cough mixture is the sixth favourite substance abused after heroin, ketamine, hypnotics, methamphetamine, and cocaine.⁴

Few studies have focused on the psychopathology associated with cough mixture abuse. Mattoo et al⁵ conducted a cross-sectional study involving 46 participants who were seeking help from an addiction clinic in North India. In all, 4 were diagnosed with schizophrenia, and 3 each were diagnosed with affective disorder or generalised anxiety disorder. Based on the data from the 2006 National Survey on Drug Use and Health, Ford⁶ reported elevated risks for major depressive disorder in teenagers misusing cough mixture. Ishigooka et al⁷ noted a hallucinatory-paranoid state and affective disorders in a series of 44 cough mixture abusers in Japan. In a Hong Kong study of 27 hospitalised cough mixture abusing patients, a significant percentage exhibited severe psychotic and mood disturbances, most commonly persecutory delusions, auditory hallucinations, and depressive symptoms.⁸

Cough mixture is the third most commonly abused substance in patients attending the substance abuse outpatient clinic at the Prince of Wales Hospital (PWH), Hong Kong.⁹ Cough mixture misuse frequently presents as mood and psychotic symptoms, but its psychopathology and natural history of the psychosis are not well known. Also, the content in the cough mixture sold in Hong Kong has not been adequately investigated. The objective of the present study was therefore to examine these factors.

Methods

Study Population

The medical records of patients, with a diagnosis of cough mixture dependence according to the ICD-10 Mental and Behavioural Disorders¹⁰ criteria who attended the substance abuse clinics of the PWH, Alice Ho Miu Ling Nethersole Hospital, and North District Hospital from October 2009 to December 2011, were reviewed. These 3 substance abuse clinics serve the entire Northeastern area of Hong Kong with a population of approximately 1.2 million, constituting about one-sixth of the total population.¹¹

The study was conducted in compliance with the Declaration of Helsinki. The study protocol was approved by the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee. Written informed consent is not required for this type of retrospective study as the collection of information is part of routine clinical care.

Data Collection

Standard clinical case records of patients attending for cough mixture misuse at the 3 clinics were retrieved for data collection. Demographic data including sex, age, education, marital status, employment, and forensic record were extracted. The history of cough mixture use, age of onset, maximum and recent amount of cough mixture abused, and history of detoxification were documented, together with the use of any other substances. The following clinical characteristics were recorded: age of onset of psychiatric symptoms, psychopathology, psychiatric diagnosis, duration between cough mixture consumption and appearance of first psychiatric symptoms, total number of hospitalisations, current treatment, and the latest Christo Inventory of Substance-misuse Services (CISS)¹² score. The CISS was developed as a single-page outcome evaluation tool completed by drug / alcohol service workers. The CISS consists of 10 items reflecting clients’ problems with social functioning, general health, sexual / substance risk- taking behaviour, psychological functioning, occupation, criminal involvement, drug / alcohol use, ongoing support, compliance, and working relationships. The ingredients of the cough mixture were determined at the first urine toxicology test.

Statistical Analysis

The data were analysed using the Statistical Package for the Social Sciences, Windows version 15.0 (SPSS Inc, Chicago [IL], US). Socio-demographic and clinical characteristics of the participants were presented as descriptive statistics. Regression analysis was employed to evaluate the clinical characteristics against CISS scores. The results are presented as mean ± standard deviation (SD).

Results

A total of 63 patients were identified as being cough mixture misusers at the 3 clinics during the study period of October 2009 to December 2011. Their case notes were retrieved and reviewed. The mean ± SD age of the group was 34.4 ± 6.2 years; 56 (89%) subjects were male; 67% were single; the mean ± SD duration of education was 8.7 ± 1.4 years; 83% were unemployed for a mean ± SD of 4.4 ± 5.7 years; and 67% used to work in the service sector. Approximately 75% had a forensic record; among these, 32% had drug- related offences, 13% had non–drug-related offences, 24% had both, and data of the remainder (6%) were missing (Table 1).

The history of cough mixture abuse of participants is shown in Table 2. They first experimented with illicit substances at a mean ± SD age of 18 ± 5 years and started cough mixture abuse at a mean ± SD age of 20 ± 5 years, reaching a mean ± SD maximum consumption of 2.3 ± 1.6 bottles/day by a mean ± SD age of 24 ± 6 years. When the participants attended the clinic, the mean ± SD amount consumed decreased to 0.6 ± 0.8 bottle/day. The favourite venue for consumption was video game centres (25%) followed by their home (21%) and the pharmacy where the drug was purchased (11%). Multiple substance abuse was also common (Table 3). Close to 16% of the participants were actively co-dependent on the so-called ‘Z-drugs’ (including zopiclone or zolpidem), and about one-quarter reported a history of dependence on Z-drugs as well as sedative hypnotics (11%), heroin (11%), or methamphetamine (13%).

The clinical characteristics of participants are shown in Tables 4 and 5. The most common psychiatric diagnoses were substance-induced psychotic disorder (67%), schizophrenia (19%), depressive disorders (11%), and dysthymia (10%). The respective mean ± SD age of onset of psychiatric symptoms and first contact with the psychiatric services was 27.6 ± 7.1 and 28.2 ± 7.1 years, and there was a mean ± SD of 3.2 ± 3.7 episodes of psychiatric hospitalisations. The mean ± SD CISS score of the 41 participants who were rated on this scale (i.e. new cases at their first visit to the clinic) was 5.7 ± 2.6. Among them, 26 (63%) participants scored ≤ 6 and 15 (37%) scored ≥ 7. Additionally, 16% of patients were in the priority follow-up group. The mean ± SD follow-up period was 6.2 ± 7.1 years.

Concerning the ingredients of the local cough mixture, dextromethorphan was only detected in 6% of the urine samples. The most frequently detected substances were promethazine (75%), pseudoephedrine (67%), codeine (60%), ephedrine (57%), zopiclone (17%), and hydrocodone (16%) [Table 6].

The current treatment regimens are shown in Table 7. Most participants (73%) were taking antipsychotic medication. Besides, 14% of the subjects were on depot medication. Additionally, 37% of participants received antidepressants, 17% were taking benzodiazepines, and 11% took Z-drugs.

Discussion

Compared with other over-the-counter cough medicines available elsewhere,^13-16 dextromethorphan was not a common ingredient in the cough medicine sold in Hong Kong. In Hong Kong, ephedrine and pseudoephedrine are frequent ingredients in commercially available cough medicines, similar to other Asian countries including India,⁵Thailand,¹⁷ Taiwan,¹⁸ Japan,^7,19 and Singapore.²⁰

Cough mixture is usually bought from pharmacies and consumed immediately. Similar to the findings of another Hong Kong study,²¹ many users reported consumption in video game centres before enjoying a round of video games. They felt cough mixture gave them superior concentration and improved their focus and confidence.

Similar to other Asian locations, in Hong Kong most cough mixture abusers are unemployed men who started taking the substance in their teenage years. In an Indian study,⁵ all 46 participants were male, with a mean age of starting cough mixture abuse of 22.7 years. In another Indian report from the area of Assam and Nagaland,²² the respective mean age of onset of abuse for the 97 patients was 17.4 and 15.8 years; all were male, over 90% were single, and 62.5% in Assam and 97.9% in Nagaland were unemployed.

It would appear that female cough mixture abusers are uncommon across Asia. In this study, 11% of the participants were women and the figure was 22.2% in a previous Hong Kong study,⁸ while none of the other mentioned Asian studies reported any female cough mixture abusers. In most countries of the world, particularly in developing countries, women’s lives are very different from those of men. Substance misuse in women is often more stigmatised and carries extreme condemnation from society. Women’s access to treatment is hindered by cultural taboos and clashes with childcare responsibilities.²³ It is likely that substance abuse among women is grossly under-reported and under-treated. A study conducted by the United Nations on substance misuse in Asian women described a series of 75 women recruited through snowball sampling in India.²⁴ The authors concluded that barriers to treatment included concerns for children unattended at home, fear of exploitation, fear of withdrawal, and lack of support systems. Heroin was the most commonly abused substance in that series, but several female cough mixture abusers were also found; however, it was not known if they received any treatment.

Similar to the results of this study, psychotic syndromes were the most frequent psychiatric co-morbidities in the Indian⁵ and Japanese studies.⁷ The frequency of psychiatric diagnoses was almost identical with that of the other local study,⁸ where diagnoses included substance- related psychotic disorders (60%), schizophrenia (15%), major depressive episode (4%), and personality disorder (4%). As expected, psychotic disorders were the most common conditions seen at the substance abuse clinics.

Ephedrine and pseudoephedrine use has been known to be related to psychoses. Since a significant proportion of the patients in this study misused multiple substances, which may have included other, more potent, stimulants such as methamphetamine, the contribution of the cough mixture ingredients to the development of psychoses remains unclear. Most participants developed a psychiatric disorder after some years of abuse. In this study, a gap of 7 years lapsed between the first use of cough mixture and the development of psychiatric symptoms. Based on the findings of this study, it is conceivable that the risk of cough mixture abusers developing a psychosis may be elevated with increased total lifetime abuse.

In the Hong Kong study,⁸ the participants admitted concomitant use of benzodiazepines (56%), cannabis (33%), cocaine (15%), heroin (15%), hallucinogens (11%), and solvents (7%). In the study by Mattoo et al,⁵ concurrent use of other substances was reported in 72% of participants, and were most commonly benzodiazepines (42%), opioids (12%), alcohol (10%), or combinations of these and / or carisoprodol (36%), a muscle relaxant with sedative properties. These figures are quite different from the findings on co-dependence of this study: 16% were concurrently dependent on Z-drugs, 3% each for methamphetamine and benzodiazepines, and 2% each for ketamine and cannabis. Zopiclone was the co-dependent substance with cough mixture most frequently detected in 17% of the participants. Zopiclone’s popularity may be explained by the fact that it is often purchased together with cough mixture in the pharmacy, often at a discount. Reflecting the change of times, the use of ketamine in this study was more prevalent than in the mid-1990s, with 38% of the participants reporting any lifetime use, although only 3% were apparently dependent on ketamine. With a lifetime dependence of 25%, Z-drugs remained the most commonly abused substances to be co-dependent with cough mixture in Hong Kong.

There are several limitations of the study. First, the participants were receiving tertiary care, thus the findings may not be generalisable to the entire substance abuse population, a significant proportion of whom might not be in treatment. Second, although the data were collected by the principal investigator, the diagnoses were established through clinical interviews and not with the aid of structured clinical interviews. Third, co-morbid multiple substance misuse is common in cough mixture abusers, it is therefore difficult to know whether a particular psychiatric condition is related to cough mixture per se, or related to other substances, or a combination of both. In fact, the composition of the cough mixture was not uniform; whether ephedrine or pseudoephedrine was the offending agent responsible for inducing psychiatric disorders remains uncertain.

Conclusions

Psychotic disorders were the most common psychiatric diagnosis in cough mixture–dependent patients attending 3 substance abuse clinics in Hong Kong. Common ingredients in local cough mixture were promethazine, ephedrine, pseudoephedrine, codeine, and hydrocodone, while dextromethorphan was infrequently detected. Co- dependence of cough mixture with zopiclone or zolpidem was often found.

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