A change in the trend in dosulepin usage following the introduction of a prescribing indicator but not after two national safety warnings.

WHAT IS KNOWN AND OBJECTIVE: The tricyclic antidepressant dosulepin has been associated with an increased risk of toxicity in overdose compared with other antidepressants. In the UK, the MHRA and NICE have issued advice on the prescribing of dosulepin, and a National Prescribing Indicator (NPI) to monitor usage was introduced in Wales in 2011. The aim of this study was to assess whether trends in dosulepin usage in Wales and NE England changed following the two pieces of safety guidance and the introduction of the National Prescribing Indicator in Wales. METHODS: Primary care dosulepin usage in the 12 months prior to and following MHRA safety advice (in 2007), NICE guideline CG90 (in 2009) and the introduction of the NPI (in 2011) was obtained. Usage was measured using defined daily doses (DDDs) per 1000 prescribing units (PUs). The trends in the 12 months prior to and following the introduction of prescribing advice and the NPI were compared using an autoregressive integrated moving average (ARIMA) model. RESULTS AND DISCUSSION: In Wales, the trend in dosulepin usage did not change significantly prior to and following the MHRA advice: -0·18 and -0·43 DDDs/1000PUs per month, respectively (P = 0·07), or prior to and following NICE CG90: -0·30 and -0·49 DDDs/1000PUs per month, respectively (P = 0·35). In the 12 months prior to and following the introduction of the NPI, the trend was -0·45 and -0·98 DDDs/1000PUs per month, respectively (P = 0·001). In NE England, the trend did not alter significantly following the NICE advice or the introduction of the NPI in Wales. WHAT IS NEW AND CONCLUSION: The trend in dosulepin usage in Wales altered significantly following the introduction of the NPI, but not after the other prescribing advice. This association, coupled with the absence of a significant change in NE England over the same period, provided some evidence of the effectiveness of the NPI in prompting a change in prescribing behaviour in Wales.

Diphenhydramine abuse and detoxification: a brief review and case report.

Many medicines available over the counter from pharmacies are known to have abuse potential, including diphenhydramine (DPH), an antihistamine with antimuscarinic properties used for the treatment of insomnia. We present a brief review of the literature describing DPH abuse, and report the case of GF, a 56 year old woman who was admitted to an inpatient addictions unit for detoxification from DPH. A literature search revealed five case reports of DPH abuse including a total of six patients, published between 1986 and 2001. All reported cases exhibited features of DSM-IV criteria for substance dependence, and there was an apparent link with antipsychotic usage. GF was treated with antipsychotics, and was using up to thirty 50 mg DPH tablets each day. She described feeling 'good and calm' and 'it stopped the tremors'. GF tolerated a gradual dose reduction schedule, and completed the detoxification programme relatively comfortably. She was discharged from the inpatient detoxification unit as planned, and had not relapsed at six months. The described case report highlights the importance of enquiring about non prescribed medication when taking a drug history. Similarly community pharmacists and GPs should be vigilant to excessive requests for DPH, particularly in patients with a psychotic illness.

Do antidepressants affect motivation in conditioned place preference?

The positive motivational effects of a range of antidepressants/neurotransmitter reuptake inhibitor compounds were studied using conditioned place preference. These agents included amitriptyline (2.5-10 mg/kg), venlafaxine (5 and 10 mg/kg), sibutramine (5 and 10 mg/kg), fluoxetine (2.5-10 mg/kg), paroxetine (5-15 mg/kg) and sertraline (2.5-10 mg/kg). Male Wistar rats were place conditioned in a three-compartment box to vehicle or drug alternately for 8 days using a 30-min pretreatment time. Control animals received vehicle only. Cocaine (5 mg/kg) was used as a positive control for the procedure. Significant place preference (P<0.05) was observed with paroxetine (15 mg/kg), fluoxetine (5 and 10 mg/kg), sertraline (2.5-10 mg/kg) and cocaine. Venlafaxine and sibutramine, serotonin/noradrenaline reuptake inhibitors, produced no place conditioning, while the highest dose of the tricyclic antidepressant, amitriptyline (10 mg/kg), produced signs of place aversion. The role of serotonin in reward pathways and differences in serotonin, noradrenaline and dopamine reuptake-inhibiting properties of these compounds may explain why only the serotonin-selective reuptake inhibitors produced place preference in this study.

Drug dependence: neuropharmacology and management.

This overview has attempted to highlight the brain regions associated with reward, and the pathways and neurotransmitters responsible for communication between these regions. Work conducted in this field has shown that stimulants and opioids, despite interactions with different receptor types and different neurotransmitter reuptake transporters, appear to share a common action on brain reward pathways. Their effects on these pathways (the distinct brain regions making up the mesocorticolimbic dopaminergic system) are predominantly mediated through changes in dopamine neurotransmission, and compounds aimed at selectively modulating these effects may form the basis of drugs to treat addiction. Other transmitters such as GABA, acetylcholine and serotonin inevitably have a role to play in reward, although at present the exact nature of their effects remains unclear. Diverging from manipulating the CNS directly as a management strategy for dependence, it might be possible to exploit the immune system to prevent administered psychostimulants penetrating the brain, but antibody saturation and specificity are problematic.