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Treatment for depression in traumatic brain injury: Cochrane find no evidence for non-pharmacological interventions

by Eleanor Kennedy @Nelllor_

This blog originally appeared on the Mental Elf site on 31st May 2016.

Traumatic Brain Injury has been associated with increased occurrence of depression (Gertler et al, 2015). Traumatic Brain Injury results from damage to the brain by external forces, such as direct impact or rapid acceleration; consequences of a traumatic brain injury may be temporary or permanent and can lead to problems with cognition, emotion and behaviour (Maas, Stocchetti, & Bullock, 2008).

The main feature of depression is either a depressed mood or loss of interest and pleasure in usual activities, or both, consistently for a two week period. Depression can present as a major risk factor for suicide after Traumatic Brain Injury.

A recent Cochrane systematic review aimed to measure “the effectiveness of non-pharmacological interventions for depression in adults and children with Traumatic Brain Injury at reducing the diagnosis and severity of symptoms of depression.”

People who experience traumatic brain injury are at an increased risk of depression.

People who experience traumatic brain injury are at an increased risk of depression.

Methods

The Cochrane Injuries Group searched eight electronic databases for randomised controlled trials (RCTs) of non-pharmacological interventions for depression in adults and children who had a Traumatic Brain Injury. For inclusion in the review, study participants had to fulfil the following criteria:

  • A history of Traumatic Brain Injury due to external forces; samples that included participants with non-traumatically acquired brain injury, such as stroke, were also included if the data allowed for separate analysis of those with Traumatic Brain Injury
  • Fulfilment of diagnostic criteria for an applicable mood disorder, such as major depressive disorder or adjustment disorder with depressive mood, based on DSM or ICD criteria
  • Presenting with clinically significant depressive symptoms based on standardised measures

The primary outcome was “the presence or remission of depressive disorders, as determined by the use of accepted diagnostic criteria (e.g. DSM-IV or ICD-10), by the use of a standardised structured interview based on such criteria (e.g. Structured Clinical Interview for the DSM Disorders), or the results of validated self- or observer-rated questionnaires of depressive symptoms.”

The secondary outcomes were:

  • Neuropsychological functioning, psychosocial adjustment, everyday functioning, quality of life, and participation
  • Medication and healthcare service usage
  • Treatment compliance, based on the proportion of withdrawals from intervention
  • The occurrence of suicide or self-harm
  • Any adverse effects of the intervention.

Results

Six studies were included in the review. Three of the studies were carried out in the USA (Ashman, Cantor, Tsaousides, Spielman, & Gordon, 2014; Ashman & Tsaousides, 2012; Fann et al., 2015; Hoffman et al., 2010), one in China (He, Yu, Yang, & Yang, 2004), one in Canada (Bedard et al., 2014) and one in Australia (Simpson, Tate, Whiting, & Cotter, 2011). Participants in all studies were over 18 years of age.

Summary of interventions in included studies

Study NParticipants Intervention Duration of Treatment Outcome measure
Ashman 2014 (Ashman et al., 2014; Ashman & Tsaousides, 2012) 77(43 completed) Cognitive Behaviour Therapy (CBT) or Supportive Psychotherapy (SPT) 16 sessions over 3 months Structured Clinical Interview for DSM-IVBeck Depression Inventory – second edition (BDI-II)
Bedard 2013 (Bedard et al., 2014) 105(76 completed) Mindfulness-based cognitive therapy (MBCT) modified to suit those with TBI 10 weekly session plus recommended daily meditation BDI-II
Fann 2015 (Fann et al., 2015) 100(86 with follow up data) CBT in person or by telephone 8 to 12 weekly sessions Hamilton Depression Rating Scale (HAMD-17)
He 2004 (He et al., 2004) 64(63 completed) Repetitive transcranial magnetic stimulation (rTMS) 4 treatment sessions each lasting 5 days, with an interval of 2 days between sessions HAMD
Hoffman 2010 (Hoffman et al., 2010) 80(76 completed) Supervised exercise training 10 weekly sessions, plus a home program BDI
Simpson 2011 (Simpson et al., 2011) 17(16 completed) Group-based CBT 10 weekly sessions Hospital Anxiety and Depression Scale (HADS)

Primary outcomes

The review reported on four comparative analyses:

  1. CBT, or a variant of CBT, vs waiting list; included a meta-analysis of three studies (Bedard, Fann, Simpson). There was no indication of a difference in depression symptoms attributable to the intervention (standardised mean difference (SMD) -0.14, 95% CI -0.47 to 0.19; Z = 0.83, p = .41).
  2. CBT to SPT; based on one study (Ashman), the difference in depression remission was not statistically supported (RR 0.76; 95% CI 0.58 to 1.00; Z = 1.96; P = 0.05) nor was the difference between groups in depression symptoms (SMD -0.09; 95% CI -0.65 to 0.48; Z = 0.30; P = 0.77).
  3. rTMS plus tricyclic antidepressants (TCA) to TCA; based on one study (He). There was a reduction in depression symptoms seen in the rTMS plus TCA group, (0.84; 95% CI -1.36 to -0.32; Z = 3.19; P = 0.001), however the difference was not considered to be clinically relevant. This was the only study to report adverse effects as two participants reported transient tinnitus with spontaneous remission.
  4. Supervised exercise and exercise as usual; based on a single study (Hoffman). There was no difference in depression symptoms between groups following the intervention (SMD -0.43; 95% CI -0.88 to 0.03; Z = 1.84; P = 0.07).

Secondary outcomes

Secondary outcomes were reported for each individual study. There was no difference in treatment compliance between intervention and comparison group in each study. One study (He et al., 2004) reported adverse effects as two participants reported transient tinnitus with spontaneous remission.

Most other secondary outcomes showed no difference between intervention and treatment groups.

There is insufficient evidence to recommend any particular non-pharmacological treatment for depression in traumatic brain injury.

There is insufficient evidence to recommend any particular non-pharmacological treatment for depression in traumatic brain injury.

Strengths and limitations

Some studies were not included because of the narrow focus of the review. The primary outcome of these studies was quality of life or psychological well-being and as such did not require included participants to have a diagnosis of depression or a particular cut-off score on a depression scale. While these may have been of interest, this is not necessarily a limitation as it allowed the authors to concentrate on a clinically relevant treatment effect for depression.

The authors found the quality of evidence to be low or very low in all comparisons, mainly due to the lack of blinding participants and personnel to the treatment. This lack of blinding could have affected the self-report depression symptom scales in particular. The authors suggested some suitable placebo treatments such as sham rTMS to imitate real TMS or a social contact intervention to compare to CBT.

Conclusion

The paucity of studies included makes it difficult to draw any firm conclusions. There was no strong evidence to support any of the interventions explored here. All of the studies are very recent which suggests there may be an increase in this kind of research.

The authors point to some implications for future research in this area, such as the careful consideration of what will be meaningful to the individual participants and the question of the suitability of RCT design for CBT interventions.

The review calls for future RCTs that compare active interventions with controls that replicate the effect of the attention given to participants during an active treatment.

The review calls for future RCTs that compare active interventions with controls that replicate the effect of the attention given to participants during an active treatment.

Links

Primary paper

Gertler P, Tate RL, Cameron ID. (2015) Non-pharmacological interventions for depression in adults and children with traumatic brain injury. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No.: CD009871. DOI: 10.1002/14651858.CD009871.pub2.

Other references

Ashman, T., Cantor, J. B., Tsaousides, T., Spielman, L., & Gordon, W. (2014). Comparison of cognitive behavioral therapy and supportive psychotherapy for the treatment of depression following traumatic brain injury: A randomized controlled trial. Journal of Head Trauma Rehabilitation, 29(6), 467–478. [PubMed abstract]

Ashman, T., & Tsaousides, T. (2012). Cognitive behavioral therapy for depression following traumatic brain injury: FINDINGS of a randomized controlled trial. Brain Impairment. Cambridge University Press.

Bedard, M., Felteau, M., Marshall, S., Cullen, N., Gibbons, C., Dubois, S., … Moustgaard, A. (2014). Mindfulness-based cognitive therapy reduces symptoms of depression in people with a traumatic brain injury: results from a randomized controlled trial. J Head Trauma Rehabil, 29(4), E13–22. [PubMed abstract]

Fann, J. R., Bombardier, C. H., Vannoy, S., Dyer, J., Ludman, E., Dikmen, S., … Temkin, N. (2015). Telephone and in-person cognitive behavioral therapy for major depression after traumatic brain injury: a randomized controlled trial. Journal of Neurotrauma, 32(1), 45–57. [PubMed abstract]

He, C. S., Yu, Q., Yang, D. J., & Yang, M. (2004). Interventional effects of low-frequency repetitive transcranial magnetic stimulation on patients with depression after traumatic brain injury. Chinese Journal of Clinical Rehabilitation, 8, 6044–6045.

Hoffman, J. M., Bell, K. R., Powell, J. M., Behr, J., Dunn, E. C., Dikmen, S., & Bombardier, C. H. (2010). A randomized controlled trial of exercise to improve mood after traumatic brain injury. Physical Medicine and Rehabilitation, 2(10), 911–919. [PubMed abstract]

Maas, A. I. R., Stocchetti, N., & Bullock, R. (2008). Moderate and severe traumatic brain injury in adults. Lancet Neurology, 7 (August), 728 – 741. [PubMed abstract]

Simpson, G. K., Tate, R. L., Whiting, D. L., & Cotter, R. E. (2011). Suicide prevention after traumatic brain injury: a randomized controlled trial of a program for the psychological treatment of hopelessness. The Journal of Head Trauma Rehabilitation, 26(4), 290–300. [PubMed abstract]

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High potency cannabis and the risk of psychosis

By Eleanor Kennedy @Nelllor_

This blog originally appeared on the Mental Elf site on 24th March 2015

shutterstock_27220114

Smoking higher-potency cannabis may be a considerable risk factor for psychosis according to research conducted in South London (Di Forti, et al., 2015).

Cannabis is the most widely used illicit drug in the UK and previous research has suggested an association between use of the drug and psychosis, however the causal direction and underlying mechanism of this association are still unclear.

This recent case-control study published in Lancet Psychiatry, aimed to explore the link between higher THC (tetrahydrocannabinol) content and first episode psychosis in the community.

To compare the impact of THC content on first episode psychosis, participants were asked whether they mainly consumed skunk or hash. Analysis of seized cannabis suggests that skunk has THC content of between 12-16%, while hash has a much lower THC content ranging from 3-5% (Potter, Clark, & Brown, 2008; King & Hardwick, 2008).

Cannabis hash and skunk have very different quantities of the active THC component.

Methods

The researchers used a cross-sectional case-control design. Patients presenting for first-episode psychosis were recruited from a clinic in the South London and Maudsley NHS Foundation Trust; patients who had an identifiable medical reason for the psychosis diagnosis were excluded. Control participants were recruited from the local area using leaflets, internet and newspaper adverts. There were 410 case-patients and 370 controls recruited.

Researchers gathered data on participants’ cannabis use in terms of lifetime history and frequency of use as well as type of cannabis used, i.e. skunk or hash. Participants were also asked about their use of other drugs including alcohol and tobacco, as well as providing demographic information.

Results

The case-patients and control participants were different in a couple of key areas (note: psychosis is more common in men and in ethnic minorities):

Case patients Control participants 
Male 66% 56%
Age 27.1 years 30.0 years
Caribbean or African ethnic origin 57% 30%
Completed high level of education 57% 90%
Ever been employed 88% 95%
Lifetime history of ever using cannabis 67% 63%

Participants with first episode psychosis were more likely to:

  • Use cannabis every day
  • Use high-potency cannabis
  • Have started using cannabis at 15 years or younger
  • Use skunk every day

A logistic regression adjusted for age, gender, ethnic origin, number of cigarettes smoked, alcohol units, and lifetime use of illicit drugs, education and employment history showed thatcompared to participants who had never used cannabis:

  • Participants who had ever used cannabis were not at increased risk of psychosis
  • Participants who had used cannabis at age 15 were at moderately increased risk of psychotic disorder
  • People who used cannabis or skunk everyday were roughly 3 times more likely to have diagnosis of psychotic disorder

A second logistic regression was carried out to explore the effects of a composite measure of cannabis exposure which combined data on the frequency of use and the type of cannabis used.Compared with participants who had never used cannabis:

  • Individuals who mostly used hash (occasionally, weekends or daily) did not have any increased risk of psychosis
  • Individuals who smoked skunk less than once a week were nearly twice as likely to be diagnosed with psychosis
  • Individuals who smoked skunk at weekends were nearly three times as likely to be diagnosed with psychosis
  • Individuals who smoked skunk daily were more than five times as likely to be diagnosed with psychosis

The population attributable factor (PAF) was calculated to estimate the proportion of disorder that would be prevented if the exposure were removed:

  • 19.3% of psychotic disorders attributable to daily cannabis use
  • 24.0% of psychotic disorders attributable to high potency cannabis use
  • 16.0% of psychotic disorders attributable to skunk use every day

These findings raising awareness among young people of the risks associated with the use of high-potency cannabis

Conclusions

The results of this study support the theory that higher THC content is linked with a greater risk of psychosis, with daily use of skunk conferring the highest risk. Recruiting control participants from the same area as the case participants meant that the two groups were more likely to be matched on not only demographic factors but also in terms of the actual cannabis that both groups were consuming.

The study has some limits, such as the cross-sectional design which cannot be used to establish causality. Also the authors have not included any comparison between those who smoke hash and those who consume skunk so no conclusions can be drawn about the relative harm of hash.

Media reports about the study have mainly focussed on the finding that ‘24% of psychotic disorders are attributable to high potency cannabis use’. This figure was derived from a PAF calculation which assumes causality and does not allow for the inclusion of multiple, potentially interacting, risk factors. Crucially the PAF depends on both the prevalence of the risk factor and the odds ratio for the exposure; the PAF can be incredibly high if the risk factor is common in a given population.

In this case, the prevalence rate of lifetime cannabis use was over 60% in both participant groups. According to EMCDDA, the lifetime prevalence of cannabis use in the UK is 30% among adults aged 15-64, so it is arguable that this study sample is not representative of the rest of the UK. The authors themselves note that “the ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies”, which is a more accurate interpretation than media reports claiming that “1 in 4 of all new serious mental disorders” is attributable to skunk use.

Future studies looking at the relationship between cannabis and psychosis should also aim to differentiate high and low potency cannabis. Longitudinal cohort studies are particularly useful as they have the same advantages as a case-control design but data about substance use could be more reliable as ‘lifetime use’ can be gathered from multiple measurements collected at a number of time points across the lifetime.

This innovative study is the first to distinguish between different strengths of cannabis in this way.

Links

Primary study

Di Forti M. et al (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study (PDF). The Lancet Psychiatry, 2(3), 233-238.

Other references

King L, & Hardwick S. (2008). Home Office Cannabis Potency Study (PDF). Home Office Scientific Development Branch.

Potter DJ, Clark P, & Brown MB. (2008). Potency of Delta(9)-THC and other cannabinoids in cannabis in England in 2005: Implications for psychoactivity and pharmacology (PDF). Journal of Forensic Sciences, 53(1), 90-94.