Recognition of tramadol abuse, dispensing practices, and opinions about its control policy among community pharmacists in Bangkok, Thailand

The protocol for this descriptive cross-sectional study was approved by the ethics committee of the Faculty of Pharmacy at Srinakharinwirot University (approval No. 007/2558). The data collection was conducted by interviewing licensed pharmacists working in community pharmacies situated in Bangkok, Thailand, from September 2015 to April 2016.

Based on the 4,794 pharmacies located in Bangkok [13], the sample size calculated using the Taro Yamane formula [14] with a 95% confidence interval was 370. A proportional quota sampling strategy focusing on utility areas in Bangkok was utilized [15]. In the present study, the capital was divided into 6 utility areas including residential, agricultural, industrial, commercial, art and cultural, and official places, which covered most of the land use in Bangkok. Each area comprised various administrative districts, which were selected by convenience sampling. In each administrative district, convenience sampling was then performed for the sample selection. The pharmacists on duty were approached by direct contact without making appointments in advance. Community pharmacists with work experience of <3 months were excluded. Then, the nature of the study including the rationale, objectives, and the interview process and time was explained to each potential participant. By implied consent, community pharmacists willing to participate in this study were interviewed to collect the information.

A structured interview form containing a checklist and short answer questions was developed to collect the data in this study. To develop and validate the interview form, content validation by 4 experts (1, provincial public health pharmacist; 2, legal expert pharmacist, assistant professor from the Faculty of Pharmacy at Srinakharinwirot University; 3, legal expert pharmacist with work experience at provincial public health office, assistant professor from the Faculty of Pharmacy at Srinakharinwirot University; 4, community pharmacist with work experience involving primary pharmaceutical services >5 years) and cognitive interview by 5 community pharmacists working in the Nakhon Nayok province were performed. The data collection consisted of 4 parts as follows.

With regard to the consistency of interview process, an interview guide was developed. The interviewers were informed about the procedure, and the interview process was rehearsed.

Descriptive statistics were used to describe the characteristics and features of the data. The basic descriptions of the quantitative variables are presented as percentage and mean ± standard deviation (SD). The questions for which there was no response were considered as missing values and omitted from the analysis.

Researchers contacted 906 pharmacies in Bangkok. During the visits, 357 pharmacies (39.4%) had pharmacists on duty. Of the 357 pharmacists, 52 refused to participate in the study, because they had insufficient time to answer the questions. Therefore, 305 pharmacists (85.4%) were interviewed to collect the information.

The present study provided 3 main findings relating to tramadol, which included dispensing practices, the recognition of tramadol abuse and the announcement of the Thai FDA control policy, and opinions about the control policy among community pharmacists in Bangkok, Thailand.

Of 185 pharmacies with tramadol availability, the formulation of fixed-dose combination (tramadol 37.5 mg plus acetaminophen 325 mg) was found to be the preferred analgesic compared with the single formulation. This might be due to the good efficacy and tolerability profile of the combined drugs. Tramadol plus acetaminophen can provide a synergistic analgesic effect [16]. One study in postoperative pain management demonstrated the comparable analgesic efficacy and fewer adverse events with a fixed-dose combination compared with tramadol 50 mg monotherapy. Therefore, the combined drug could reduce tramadol consumption by 24% [17]. Moreover, as superior to ad hoc dose ratios, the fixed-ratio combination of tramadol plus acetaminophen provided standardized reproducible improvement in pain scores and side effect profiles in multicenter randomized controlled trials for the management of some chronic pain conditions [18]. Moreover, community pharmacists participating in this study revealed that most young people requested tramadol by using phrases such as “green–yellow medicine”, “tramadol”, “green–yellow capsule”, and “green–yellow analgesics”, which reflects the preferred abuse formulation as a single rather than a combined drug. This indicated the high abuse potential of the single drug formulation among Thai teenagers, which is one reason for the withdrawal of tramadol from the list of available drugs in many pharmacies involved in the present study.

We found that tramadol was dispensed to some customers as a single drug and combined with acetaminophen to others, indicating that the 2 formulations should be available in pharmacies. The dispensed amounts were mostly 10–20 tablets/capsules per customer, which was consistent with the rule of limitations on sale amounts (not more than 20 tablets/capsules per case) as established by the tramadol control policy. Tramadol was dispensed to alleviate moderate-to-severe pain as recommended by the Thai FDA [3]. Pharmacists suggested various dosage regimens of tramadol to customers depending on their assessment of individual customers, but did not exceed the maximum recommended dosage. Most pharmacists explained the common side effects, indicating good dispensing practice related to this issue. However, only a small number of pharmacists provided an explanation of special precautions related to drug interactions. Tramadol has the potential to interact with numerous drugs such as tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and drugs affecting cytochrome P450 2D6 (CYP2D6) activity [19, 20]. We recommend pharmacists remind themselves of the possible harmful effects of drug interactions and inform patients about the interactions before dispensing tramadol.

Pharmacists received information about tramadol being a drug of abuse among Thai youth from various sources, but especially from television news and social media. This information reminds pharmacists to realize the current potential for abuse and encourage them to prevent problems. However, the widespread distribution of this information probably leads to imitation of the behavior by teenagers. The authorities could directly publicize more information about the dangers of tramadol abuse to the community through effective communicative channels, including television, social media, and newspapers.

Most pharmacists knew about the announcement of tramadol control policy, mostly through the letter from the Thai FDA, indicating effective public relations. However, to remind community pharmacists, the announcement period should be longer and continuously supported through other appropriated sources, such as social media, professional associations, and educational institutes.

Most of the community pharmacists (70.5%) had encountered children and teenagers asking for tramadol at their pharmacies and suspected intended tramadol abuse. This finding is consistent with the findings of Zabihi et al. that >55% of the customers seeking tramadol were aged <18 years [21]. The pharmacists in this study refused to supply tramadol to young customers because of the high risk of intended drug abuse. Some pharmacists also noticed that if tramadol was dispensed to one teenager, others would also request tramadol from their particular community pharmacy. This appears consistent with a previous report that the motivations of peers played a pivotal role in substance abuse among adolescents [22].

The results from the interviews indicated that most community pharmacists dispensed tramadol in accordance with Thai FDA control policy compliant with the aspects of age and quantity limitations. However, screening the tendency for tramadol abuse by customers using other questions, as mentioned in the report by Zabihi et al. [21] including “What are you using tramadol for?”, “Have you ever needed to increase your tramadol dose without checking with your physicians?” and “Have you ever felt that you could not stop or decrease your use of tramadol?”, could be useful to reduce or avoid tramadol abuse in the community.

Most of the community pharmacists surveyed in this study considered that, in general, following the Thai FDA control policy was practical. Santisetthsin and Thananithisak used questionnaires sent by mail to pharmacists in Bangkok and also found that community pharmacists agreed with the tramadol control policy [23]. Although the methodology for data collection in this study and that by Santisetthsin and Thananithisak was different, the findings from both studies suggested that most pharmacists working in Bangkok accepted the implementation of the Thai FDA policy to control the sale of tramadol in community pharmacies. We found that the pharmacists participating in the present study had various opinions about whether or not the Thai FDA rule could reduce tramadol abuse. This, at least partly, reflected their lack of confidence with the effectiveness of the policy. To strengthen its implementation, an annual assessment of policy achievement to reduce tramadol abuse is proposed, such as assessment of any reduction in the number of people hospitalized because of tramadol intoxication.

The scheduling of tramadol as a controlled substance is a method to diminish abuse problems [23]. A study conducted in Kentucky and Arkansas established a reduction in the number of cases of tramadol consumption and exposure to toxicity following its addition to the schedule of controlled substances [24]. However, community pharmacists in Thailand from both the present study and that by Santisetthsin and Thananithisak mostly disagreed with rescheduling tramadol as a prescription-only medicine [23]. They opined that the lack of availability of tramadol in pharmacies would diminish the potential drug accessibility by some patients with medical necessity. Currently, tramadol remains available in community pharmacies as the Narcotics Control Board (NCB) Secretary General noted that a sales ban would likely affect the general public [12].

School-based education is considered an important tool to prevent drug abuse [25]. Based on the opinions of many pharmacists participating in the present study, social regulations are effective strategies to decrease the tramadol abuse. Raising awareness at school and in the community on the prevention of initial tramadol use by providing education to children and their parents is critical. Any community pharmacists acting as retailers of drugs of abuse must be strictly and legally prosecuted. Finally, cooperation between adolescents, their families, teachers, health care providers, and the government is necessary to solve this critical problem.

The present study offers important and unique data related to the perspective of community pharmacists on tramadol usage and the current control policy related to the dispensing of tramadol in the Thai capital. We consider that it contributes to a better understanding of the use and abuse of tramadol in this region, which may be of benefit to pharmacists and other health care professionals nationwide. In addition, policy makers may consider the research evidence to improve control policy to minimize the misuse or abuse of tramadol in Thailand.

The sampling technique used is a limitation of the present study. A proportional quota sampling strategy focused on the utility areas of Bangkok was used first for probability sampling, followed by a convenience sampling strategy. This method may not represent data accurately for the entire population of community pharmacists in Bangkok. The possibility of over- and under-representation of samples in some areas may affect the quality of data collection. However, we attempted to minimize this limitation by using a proportional quota sampling in the first step to cover all the utility area of Bangkok. Other potential limitations included unachieved target sample sizes, recall bias, and study locations. There were just 305 participants or 82.4% of the expected sample size. Based on the study plan, it was proposed that we could get the data from 1 pharmacist at each pharmacy. However, some pharmacists were not on duty during our visit time, which might be a result of the convenience sampling without making appointments in advance. To diminish possibility of recall bias, resulting from direct interviews with an individual pharmacist to obtain information on their past experiences, the researchers only asked for information recalled from within the previous 3 months. In the aspect of the location limitation, the study was conducted in Bangkok, which is considered to be a high-risk region for widespread drug abuse. Therefore, the findings from this city alone with its unique culture might limit the generalizability of our findings.