Cluster Headache in Subjects With Substance Use Disorder: A Case Series and a Review of the Literature.

OBJECTIVE: To describe a case series of 7 patients presenting cluster headache (CH) criteria and a substance use disorder, reported to a French Addictovigilance center. Then, to assess clinical, pharmacological, and neurobiological linkages between substance use and CH onset. BACKGROUND: CH patients are presenting a higher prevalence of comorbidities, among which the use of psychoactive substances, licit or illicit, have been explored by a few authors. Recently, 3 cases of CH in patients seen in the hospital-based addiction care center have been reported to the Toulouse addictovigilance center. METHODS: Other cases have been identified in the same tertiary hospital after a collaborative investigation done with the departments of neurology and psychiatry and included in the case series. A narrative review was performed to assess the potential of psychoactive substance consumption to induce or facilitate CH. RESULTS: From 2016 to 2018, 6 males and 1 female aged between 26 and 54 years old, presenting CH criteria and a substance use disorder, were included in our case series. Among substances used, there are: (1) daily use of tobacco and alcohol in 5/7 subjects; (2) daily or almost daily use of cocaine in 5/7 subjects; (3) regular use of cannabis before attacks beginning in 4/7 subjects; and (4) opioids, as a substitutive medication or abused, in 5/7 subjects. The intranasal route administration is reported by all the subjects and precedes the beginning of attacks for 5/7 subjects. CONCLUSIONS: We have found a CH prevalence of 0.9% in our studied population, while it is estimated at 0.1% in the general population. The coexistence of cluster headache and addiction behaviors reflects possible common neurobiological pathways, which would include the hypothalamus. Research could be conducted on the potential of hypothalamic therapeutic targets.

Psychotic Decompensation During Nalmefene Treatment in a Patient With Schizoaffective Disorder: A Case Report.

Objective: Nalmefene is a kappa-opioid receptor agonist/antagonist which is currently prescribed to reduce heavy drinking days. Adverse events (AEs) have previously been described in trials, but these trials excluded patients with psychiatric comorbidities. This is important as psychiatric disorders are frequently associated with alcohol use disorders; therefore, the specific AEs in this population should be investigated. Methods: Here, we describe the case of a patient with diagnosed alcohol use disorder and schizoaffective disorder who received treatment with nalmefene. Results: The patient showed decompensation of psychotic symptoms after two doses of medication, consisting of auditory hallucinations, delusions, and ideas of persecution. The symptoms improved two days after treatment discontinuation. Conclusions: This case indicates that the AEs of nalmefene should be specifically investigated in patients with psychiatric disorders.

Early signal of diverted use of tropicamide eye drops in France.

AIMS: Tropicamide is a mydriatic drug used as eye-drops for diagnostic or therapeutic purposes. From 2013, a diverted use by intravenous route has been suspected in Eastern Europe in opioids users. To date, no signal of misuse has been identified in France. The aims of this study were to investigate any early signals of a diverted use of tropicamide eye drops and to collect information regarding motives for the misuse and tropicamide-induced effects. METHODS: Information was obtained at three levels: (1) at regional level (Midi-Pyrénées area), from reimbursement data and pharmacists' reports on suspicious requests; (2) at national level: from reimbursement data and prescriptions suggesting possible abuse from the OSIAP (Ordonnances Suspectes, Indicateur d'Abus Possible) survey; and (3) at international level: from VigiBase® reports and Web sources. Beta-blocker eye-drops were used as comparators. RESULTS: In France, in 2014-2015, 17 (0.91%, 95% CI [0.53-1.46%]) falsified prescriptions involving tropicamide were identified in the OSIAP survey (compared with 0%, 95% CI [0-0.19%] for beta-blockers). Moreover, 37 other suspicious prescriptions were presented in 2015 (notified in 2016). In Midi-Pyrénées, seven patients aged 35-49 were reimbursed for 19-45 vials of 10 ml, in a year. Since September 2014, the regional Addictovigilance Centre has received 91 notifications of suspicious requests to obtain tropicamide. In VigiBase® , two cases were identified but none in France. An increased interest in tropicamide-related Internet searches was observed from Russia and Ukraine. CONCLUSIONS: These results represent the first early warnings of a tropicamide diverted use in France. Tropicamide abusers would seek euphoria or hallucinations. The high doses involved in intravenous administration could lead to serious complications.

[Psychoactive effects of 'legal high': About lysergic acid amide (LSA)]. / Effets psychoactifs des « legal high ¼ : à propos de l'acide lysergique amide (LSA).

Lysergic acid amide (LSA) is a natural psychoactive substance consumed as a psychedelic drug. In 2016, 4 cases were reported to the Toulouse Addictovigilance Centre, resulting in unintended psychic effects and led to a hospitalisation in 2 cases. Other cases of serious LSA intoxication are published, including a death. It is important to inform about the risks related to LSA consumption, a substance which is freely available and sometimes hidden behind various plant names.

GPs' practices when prescribing buprenorphine in primary care: A survey among the Sentinelles network.

INTRODUCTION: France is a leading country for opioid agonist treatment providing, with a predominance of buprenorphine. General practitioners (GPs) are the main prescribers of buprenorphine, but they seem to be less involved over the last 10 years. This work is the second part of a larger study analysing buprenorphine prescribing among French GPs working in primary care, and aims to describe GPs' practices when prescribing buprenorphine. METHODS: This is a cross-sectional study conducted in France from March to July 2021 among a sample of GPs in the Sentinelles network, a national epidemiologic surveillance system. Data about the last situations of initiation and renewal of buprenorphine were collected. RESULTS: Among the 237 participants (34.3% response rate), 156 responded to the questionnaire about the last situation of renewal and 41 about the last situation of initiation. The last initiation occurred more than 12 months earlier for 46.3% of respondents, whereas the last renewal occurred less than 1 month ago for 68.6%. There was an over-representation of the male gender among the patients who were consulting (initiation 70.7%, renewal 68.6%). A majority of patients had an illicit opioid use disorder (initiation 78.0%, renewal 82.7%). Overall, GPs were involved in the general care of patients with opioids use disorder and in opioids harm reduction (initiation 87.8% and 82.9%, renewal 88.5% and 51.9%). CONCLUSION: Among buprenorphine prescribers, initiations were infrequent unlike renewals and involved mainly illicit opioid users.

Increase of cannabis and cocaine use by pregnant women in France from 2005 to 2018: Insights of the annual cross sectional OPPIDUM survey.

CONTEXT: Substance use disorders during pregnancy are associated with antenatal, neonatal and long-term adverse drug reactions in children. The aim of this study was to describe, using data from OPPIDUM survey, the evolution of illicit substance use or diverted prescription drug use among pregnant women visiting French addiction care centres from 2005 to 2018. MATERIAL AND METHOD: The current study focused on women of childbearing age (15-44years old) identified as pregnant, and included in the OPPIDUM survey from 2005 to 2018. OPPIDUM is a French nationwide survey repeated each year since 1995, which anonymously collects information on drug abuse and dependence observed in patients recruited in addiction care centres. Patterns of illicit substance use, psychoactive medications, and opioid maintenance treatment (OMT) were described over time (by period of 2 years) and changes between 2005-2006 and 2017-2018 were investigated. RESULTS: From 2005 to 2018, 784 pregnant women were included in the OPPIDUM survey (median age 28, interquartile range (IQR): 25-33). The proportion of women using exclusively cannabis (1.2% vs. 17.1%, P=0.0004) and cocaine (including crack) use (4.7% vs. 14.3%, P=0.0384) significantly increased over the period. Considering the first substance reported as leading to dependence, heroin significantly decreased (78.8% vs. 50.0%, P=0.0002) whereas cannabis significantly increased (5.9% vs. 25.7%, P=0.0005). CONCLUSION: This study highlighted an important change of patterns of drug use by French pregnant women over a 14-year-period. Health professionals must be aware of these changes to adapt prevention and care among women of childbearing age and pregnant women.

Prescribing buprenorphine for opioid use disorder in primary care: A survey of French general practitioners in the Sentinelles network.

INTRODUCTION: Although opioid substitution coverage in France is high and patient care with buprenorphine is mainly managed by general practitioners (GPs), buprenorphine sales have been decreasing since 2011, suggesting that French GPs are prescribing less buprenorphine. Yet this possible change in GP practices has not yet been investigated. This study aimed to examine primary care GPs' opinions about buprenorphine and habits related to prescribing buprenorphine. METHODS: The study team conducted a cross-sectional survey from March 2021 to July 2021 among a sample of GPs in the Sentinelles network, a French epidemiologic surveillance system based on primary care practitioners. The study collected information about substance use disorder (SUD) training, opinions on buprenorphine, and habits related to buprenorphine prescription were collected (initiation and renewal within the past two years). FINDINGS: Among the 237 participants (34 % response rate), 15.2 % reported having had specific training for SUD management. A majority reported a very positive (16 %) or positive (63.7 %) opinion of buprenorphine. Most participants agreed (61.2 %) or strongly agreed (31.2 %) that buprenorphine was efficacious in the treatment of illicit opioid use disorder. Of the 206 GPs who reported having treated patients with opioid use disorder in the past two years, 47 (22.8 %) had initiated a buprenorphine prescription, whereas 177 (85.9 %) had renewed a buprenorphine prescription. Previous SUD training was associated with initiating buprenorphine (OR 4.66; 95 % CI [2.15-10.08]), while female gender was associated with not initiating buprenorphine prescribing (OR 0.46; 95 % CI [0.22-0.98]). CONCLUSION: A sample of French GPs who work in primary care has a positive view of buprenorphine, but the absence of SUD training among this population may be a barrier to their prescribing buprenorphine.

[Substance use among young people: From medicine to illicit substances]. / Consommation de substances chez les jeunes : du médicament aux substances illicites.

This paper aims to present the main information presented at the 9th meeting about addictovigilance in 2016 by three healthcare professionals and addiction experts on the issue of substance use in young people. The results of surveys conducted in general population and of specific addictovigilance investigations, bring information on consumption data and use patterns in this population of 11-25years of age. The provision of care, mainly constituted by the Young consumers' consultations, has to adapt to diversified practices, ranging from experiment to substance use disorders, which vary over time and often hidden.

Gabapentinoid Abuse in France: Evidence on Health Consequences and New Points of Vigilance.

Introduction: Gabapentinoid drugs (gabapentin and pregabalin) are widely used worldwide for epileptic and pain disorders. First signals of gabapentinoid abuse occurred in the last decade. This study aims to describe clinical characteristics of gabapentinoid use related disorders and health consequences in France. Materials and Methods: We designed a multisource investigation reviewing data reported to the French Addictovigilance Network (FAN) with pregabalin and gabapentin from 2010 to 2019. Information was obtained through the analysis of Spontaneous Reports (SRs) notified by health professionals and the pharmacoepidemiological surveys OSIAP (suspicious prescriptions forms indicators of potential abuse), OPPIDUM (observation of illicit drugs and misuse of psychotropic medications), DRAMES (death related to prescription drugs and other substances), and DTA (toxic deaths due to analgesics). Results: Over 2010-2019 period, were collected: (i) 265 SRs (258 pregabalin; 7 gabapentin); (ii) 816 forged prescription forms (805 pregabalin, 10 gabapentin, 1 involving both drugs); (iii) 145 cases of gabapentinoid use in people who use drugs (121 pregabalin; 24 gabapentin) and (iv) 31 cases of gabapentinoid-related deaths (25 pregabalin; 6 gabapentin). Risk factors of gabapentinoid abuse were opioid use disorders or psychiatric history, but cases of primary abuse in subjects without any substance abuse history were observed. Adverse outcomes concern almost exclusively pregabalin, with coma, dyspnea, convulsion, and conduction disorders. Treatment demands increased from 10.6% in 2018 to 23.1% in 2019, with pregabalin cited as the first substance leading to addictological care in the 2019 OPPIDUM survey. Gabapentinoid-related deaths increased over time. Pregabalin has become the first drug mentioned in forged prescriptions in 2019 (23.8% of OSIAP), while it ranked at the 15th position in 2017 (2.6%). Discussion: This study shows the importance of addictovigilance monitoring for gabapentinoids. Addictovigilance data helped to make visible the gabapentinoid-abuse related health harms (hospitalization for serious neurologic, psychiatric or cardiac effects, requests for addictological support and deaths) and to confirm the intrinsic abuse potential of pregabalin. These data highlight new points of vigilance considering observed primary abuse. At this point in France, the risk of abuse and related complications is very apparent with pregabalin. Still, it is identical to that observed elsewhere with gabapentin.

Doctor shopping of opioid analgesics relative to benzodiazepines: A pharmacoepidemiological study among 11.7 million inhabitants in the French countries.

BACKGROUND: The abuse of prescription opioids and its subsequent consequences is an important public concern particularly in the USA. The literature on opioid analgesic abuse is scarce. OBJECTIVE: We assess the extent and risk of opioid analgesics abuse relative to benzodiazepines (BZD) using the doctor shopping method, taken into account the pharmacological characteristics (dosage, route of administration, extended or immediate release). METHODS: We used SNIIRAM database covering 11.7 million inhabitants. All individuals with at least one reimbursement for non-injectable opioid analgesic or BZD in 2013 were included. Opioids for mild to moderate pain and for moderately severe to severe pain were studied. The Doctor Shopping Quantity (DSQ) is the quantity obtained by overlapping prescriptions from several prescribers. The Doctor Shopping Indicator (DSI) is the DSQ divided by the total dispensed quantity. RESULTS: The strong opioid analgesics have the highest DSI (2.79%) versus 2.06% for BZD hypnotics. Flunitrazepam ranked first according to its DSI (13.2%), followed by morphine (4%), and zolpidem (2.2%). The three-strong opioids having the highest DSI were morphine, oxycodone and fentanyl (respectively 4%, 1.7% and 1.5%). The highest DSI was observed for the highest dosages of morphine (DSI = 8.4% for 200 mg) and oxycodone (DSI = 2.8% for 80 mg). The highest DSI for fentanyl was described with nasal and transmucosal forms (4.1% and 3.3% respectively). The highest DSI for morphine was described for extended-release (4.1%). CONCLUSION: There is a need to reinforce surveillance systems to track opioid misuse and to increase awareness of healthcare professionals.

Disproportionality Analysis for the Assessment of Abuse and Dependence Potential of Pregabalin in the French Pharmacovigilance Database.

BACKGROUND AND OBJECTIVE: Pregabalin abuse and dependence has been increasingly described; however, it is not described in France. Our study aimed to investigate the abuse and dependence potential of pregabalin by a disproportionality analysis, in the French Pharmacovigilance Database (FPVD), in comparison with amitriptyline and clonazepam. METHODS: We performed a case/noncase study in the FPVD. Between January, 1 2010 and December, 31 2015, we identified cases of abuse and or dependence (excluding isolated withdrawal syndromes) using MedDRA (Medical Dictionary for Regular Activities) terms. Exposure to pregabalin was defined as the mention of pregabalin in the report. Clonazepam was used as positive control and amitriptyline as negative control. RESULTS: Among the 184,310 reports in the database, 521 were abuse or dependence cases. Exposure to pregabalin was found in eight (1.5 %) of them. We did not find any significant association between exposure to pregabalin and drug abuse or dependence: reporting odds ratio (ROR) = 1.1 95 % confidence interval (CI) (0.6-2.3). ROR for clonazepam was 5.7 95 % CI (3.5-9.2). No case of an amitriptyline-related abuse or dependence was recorded in the FPVD. CONCLUSIONS: The first cases of pregabalin-related abuse or dependence reported in France occurred later than in other European countries, since none had been described before 2010. This analysis in the FPVD did not find a higher proportion of abuse/dependence with pregabalin in comparison with other drugs. Considering evidence of pregabalin abuse worldwide, this analysis underlines the limitations of spontaneous reporting system in the field of addictovigilance.