Antidepressants: check tolerability and depending on response, work through the dose range over several weeks; when stopping, do so over a fortnight or so. All still accurate advice?
Kaleidoscope reviews two papers, each of which takes a different time-point of such medication use. A dose-response meta-analysis of 77 double-blind randomised controlled trials covering almost 20,000 participants found that for SSRIs the dose-efficacy curve increased to a dose-equivalent of 20-40mg of fluoxetine, and thereafter levelled and declined. In other words, a maximum response was seen at the lower end of the dose range, with primarily side-effects after that. This fits with PET data that shows about 80% of serotonin receptors occupied at low doses. The higher end of the prescribing spectrum would appear to bring greater harms with considerably fewer gains.
There has been increased recognition of the problems discontinuing antidepressants can bring, debate as to whether or not this constitutes ‘withdrawal’ and that such medications could be addictive for some. The second reviewed paper argues convincingly against this, not least as antidepressants are not linked with any of the drug-seeking behaviour one typically assigns to addiction, and notes how discontinuation symptoms are low in trials where medications are replaced by placebo (so the individual thinks they are still getting the medication). Nevertheless, the area remains understudied, and the issue is a real one for many.
It has been said that alcohol is a perfect solvent – it dissolves marriages, families and careers – and so to two papers that I think many of you will relate to, on doctors, stress and booze.
Saliva samples from 250 first-year junior doctors were explored for telomere attrition and any associations with their life experiences. Telomeres are tandem DNA nucleotide repeats found at the end of chromosomes, maintaining the stability and integrity of the genome. They decrease with cell replication, and below a certain level a cell will stop replicating. Stress has been shown to exacerbate this attrition and is linked to a number of health conditions including heart disease and increased premature mortality. Surveys were completed every three months for a year, exploring well-being, working hours, sleep, and outside stressful events; saliva samples were taken at the start and end of the year. Longer working hours were associated with significantly greater telomere loss across the year. Shockingly, the mean attrition was six times greater than that seen in the general population across a similar time frame.
The second paper report on that dubious ‘cure’ for stress – alcohol – in the first study to explore a wide range of health problems and work risk factors in UK medics. A total of 417 doctors completed the survey; 52% were women, and 49% were consultants. Of these, 44% binge-drank alcohol, with 5% meeting criteria for alcohol dependency. Sleep problems were reported in 20–61% (12% moderate–severe insomnia) and 69% experienced fatigue. The results are concordant with the fact that 55% of doctors report suffering from burnout or emotional exhaustion: something’s gotta change folks.
- Rates of cellular telomere loss – which increase with stress and are associated with poor health outcomes – have been shown to double in junior doctors compared with the general population.
- The broadest survey of health problems in UK medics has reported that over half were suffering from burnout or emotional exhaustion.
- A meta-analysis of almost 80 randomised controlled trials has shown that maximum SSRI responses are achieved at the lower end of the dose range.
- False, the rate of loss was six times greater in junior doctors.
- True, sadly.