Interventions for the management of fatigue in adults with a primary brain tumour

Key message

We do not know whether any treatments are effective in the management of people with primary brain tumour and high fatigue due to finding only three trials each with a low number of participants.

What is a primary brain tumour?

A primary brain tumour is a cancer that began in the brain rather than spreading from other parts of the body. Brain tumours are graded as high grade and low grade; high-grade tumours are made up of very abnormal cells that grow quickly, whereas low-grade tumours are made up of abnormal cells that grow slowly. Fatigue (tiredness) is common in people with a primary brain tumour. This may be due to the tumour, its treatment or the use of other medicines, such as antiepileptic medicines (which are used to treat seizures (fits)). It may also occur with other symptoms such as sleep disturbance, thinking problems and emotional distress.

What did we want to find out?

We wanted to find out if treatments to help manage fatigue may improve a person's quality of life, their ability to tolerate cancer treatment (which in itself is associated with fatigue), and their ability to carry out social and day-to-day activities.

What did we do?

In April 2022, we searched four medical databases. We found three clinical trials that were eligible for inclusion. The three trials investigated the use of three medicines (modafinil, armodafinil and dexamfetamine sulfate) in adults with a primary brain tumour and high levels of fatigue. These medicines promote wakefulness.

What did we find?

The three included trials found no evidence of a difference between the medicine and placebo (a dummy treatment) in treating fatigue at the point the trials ended. It is possible that this could be due to two trials not reaching their planned number of participants.

What were the limitations of the evidence?

With only three included trials, and the lack of positive findings, we do not currently know whether any treatments are effective in the management of people with primary brain tumour and high fatigue. Further, there were no included studies of non-medicine interventions, such as talking therapy and exercise. More high-quality studies are needed that enrol adults with primary brain tumours and high fatigue. We found three ongoing studies that are investigating non-medicine interventions that might offer some helpful results.

How up-to-date is this evidence?

The evidence is current to April 2022.

Authors' conclusions: 

There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.

Read the full abstract...

Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.


To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.

Search strategy: 

For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and for ongoing trials.

Selection criteria: 

We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.

Data collection and analysis: 

Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.

Main results: 

The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies.

In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies.

There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.