Depression in adolescents, renal agents in diabetes and skin cancer in RA: journals update March 2016

A round-up of recent research of interest to GPs


GPs are well used to diagnosing and treating depression in adults. However, few tools exist for identifying it in adolescents. This paper describes three key questions that could be used to identify which young people need further assessment for possible depressive illness.

Study design
This was a cross sectional, multicentre validation study in primary care in Norway and Denmark. The aim was to determine if three key questions are valid for identifying depression among adolescents:

  • During the past month, have you often been bothered by feeling down, depressed or hopeless?
  • During the past month, have you often been bothered by little interest or pleasure in doing things?
  • Is this something you would like help with?

Key findings
During a telephone call with a GP, 294 study participants, aged 14-16 years, answered the three key questions, then undertook a Composite International Diagnostic Interview (CIDI) for psychiatric diagnosis.

The CIDI was used as a gold standard for comparison and 33 adolescents were identified as having a current depressive episode.

The results from both were analysed, with the three questions found to be reliable when tested against the CIDI.

Answering ‘yes’ to two screening questions had a sensitivity of 82% and a specificity of 77%, but adding the ‘help’ question increased the accuracy, giving a specificity of 98%. The positive predictive value when using the three questions was 31%, but the negative predictive value was 97%.

Implications for GPs
With ever-increasing time constraints, GPs need access to quick and accurate diagnostics. This study shows that three short questions could be used verbally in primary care to identify depression in those aged 14-16 years.

The questions could be used at any time during a consultation if the GP suspects depression, for example, in a young person who has somatic symptoms.

Br J Gen Pract 2016; DOI: 10.3399/bjgp16X683461


Benzodiazepines (BZDs) are commonly prescribed for anxiety and sleep disturbance. Although they are often very effective, they carry a significant risk of dependence.

This study carried out in Spain highlights interventions suitable for use in primary care.

Study design
This three-arm, multicentre cluster randomised trial assessed two structured interventions for cessation of BZDs compared with usual care.

The GPs allocated to the intervention arms attended a workshop on BZD discontinuation, then used a structured educational interview with either written stepped dose reductions individualised for each patient, or regular (every two to three weeks) follow-ups in primary care.

Key findings
The NNT for one patient to discontinue BZD use at 36 months was seven for the written instructions group and six for the regular follow-up group. The interventions used did not appear to increase anxiety or depression symptoms, or cause sleep disturbance.

Implications for GPs
This study showed favourable outcomes even with minimal GP contact time, indicating that written dose reduction instructions could be given to patients without the need for frequent follow-up appointments.

Br J Gen Pract 2016; DOI: 10.3399/bjgp16X683485


Diabetes mellitus and hypertension are commonly found together, increasing the patient’s risk of vascular injury. Choice of drug to use first is probably not as important as achieving optimal BP control.

Study design
The researchers undertook a systematic review and meta-analysis including 19 RCTs with a combined total of 95,910 patient years of follow-up. The trials included comparisons of ACE inhibitors or ARBs with calcium-channel blockers, thiazide diuretics or beta-blockers.

The authors sought evidence for superiority of renin-angiotensin system (RAS) blockers for the prevention of cardiovascular and renal events in patients with diabetes.

Key findings
A similar risk of death, cardiovascular death, MI, angina, stroke, heart failure, revascularisation and end stage renal disease was found in diabetic patients treated with RAS blockers when compared with those treated with other antihypertensive drugs.

Most of these patients had no proteinuria or microalbuminuria. Therefore, the study did not show any superiority of RAS blockers for patients with diabetes.

Implications for GPs
Good BP control for patients with diabetes is important for reducing the risk of micro- and macrovascular complications.

Although some of these patients may have comorbid indications for RAS blockers, such as heart failure or chronic kidney disease with proteinuria, for most, lowering their BP is more important than any concern regarding which drug to choose.

This may be particularly useful to note when patients return with side-effects or difficulties taking their medication.

BMJ 2016; 352: i438


SSRIs and SNRIs are commonly prescribed antidepressants, but they are not without side-effects and possible harm.

Study design
The researchers conducted a systematic review and meta-analysis, covering 70 trials with a total of 18,526 patients. The authors aimed to access as much patient data as possible, using clinical study reports, individual patient narratives and listings of individual adverse events.

Key findings
Some serious harm events were only found within individual patient listings or narratives in appendices.

Summary trial reports did not contain information regarding all of the adverse events that occurred. There were also errors in some study designs, potentially leading to under-reporting of serious harm.

ORs were calculated using the data extracted. There was no significant difference in suicidality or mortality in adult patients, although there was an increase in aggression and akathisia, but an increased suicidality risk for children and adolescents was confirmed.

The ORs for adults were 0.81 for suicidality, 1.09 for aggression and 2.00 for akathisia. For children and adolescents, the corresponding values were 2.39, 2.79 and 2.15. There were no child or adolescent deaths.

Implications for GPs
Patients have a right to be informed about the possibility of side-effects with prescribed medication, but unfortunately, we cannot always rely on the original trials to provide reliable data.

This study confirms the potential harmful side-effects of antidepressants in children and young people (see box 1). GPs should consider the level of support available and monitor patients carefully for any side-effects.

BMJ 2016; 352: i65

Box 1 SSRIs and SNRIs

Authors’ findings and recommendations

  • 'Despite all the limitations we identified in the trials and in the clinical study reports, we found a doubling of both suicidality and aggression in children and adolescents.’
  • ‘Minimal use of antidepressants in children, adolescents and young adults, as the serious harms seem to be greater, and as their effect seems to be below what is clinically relevant.’
  • ‘Alternative treatments, such as exercise or psychotherapy, may have some benefit and could be considered, although psychotherapy trials also suffer from publication bias.’


TNF inhibitors are commonly used to treat rheumatoid arthritis (RA) and other inflammatory conditions.

Some concerns have been raised regarding a possible increased risk of cancer with these treatments, in particular, non-melanoma skin cancer (NMSC).

This study gives evidence for an increased risk of squamous cell carcinoma (SCC), but the main findings are an increased risk of basal cell carcinoma (BCC) and SCC for all patients with RA, even if they have not been treated with TNF inhibitors, suggesting that it is having the disease itself which most increases the risk.

Study design
Patients in Sweden with RA were identified from national registers and separated into two groups, biologics naive or starting TNF inhibitors within a defined period.

These groups were matched with general population comparator cohorts and compared for incidence of BCC or SCC (in situ or invasive), using Cox regression to produce hazard ratios.

Key findings
Patients with RA who are naive to biologics are at a 20% increased risk of developing BCC and a near double risk of developing SCC, compared with the general population.

When treated with TNF inhibitors, their risk of SCC rises by a further 30%, but there is no significant rise in the risk of BCC.

Implications for GPs
Patients need to be informed and reminded of their risk of NMSC, and given sensible skincare advice. GPs should consider a possible diagnosis of BCC/SCC when patients with RA present with new skin lesions.

BMJ 2016; 352: i262

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