Effectiveness Not Established

Modafinil/Armodafinil

for Sleep-Wake Disturbances

Modafinil is a psychostimulant effective in the treatment of excessive sleepiness associated with narcolepsy and in people with shift-work sleep disorder. It is used to increase wakefulness and capacity for attention, to brighten mood, and to enhance memory. Modafinil comes as a tablet for oral intake and has been evaluated in patients with cancer for fatigue and cognitive impairment.

Armodafinil is a similar drug with a slightly different chemical configuration also used as a wakefulness-promoting agent. Armodafinil reaches peak concentration in the blood later after administration than modafinil.   Armodafinil has been studied for its effect on fatigue, anxiety, sleep-wake disturbances, and depression in people with cancer.

Research Evidence Summaries

Heckler, C.E., Garland, S.N., Peoples, A.R., Perlis, M.L., Shayne, M., Morrow, G.R., . . . Roscoe, J.A. (2016). Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: A randomized placebo-controlled trial. Supportive Care in Cancer, 24, 2059–2066.

Study Purpose

To assess the combined and comparative effect of cognitive behavioral therapy (CBT) and armodafinil to improve sleep and daytime functioning in survivors of cancer.

Intervention Characteristics/Basic Study Process

Participants were randomized to (a) CBT-I and placebo, (b) CBT-I and armodafinil 50 mg b.i.d., (c) placebo BID, or (d) armodafinil 50 mg BID. All received written sleep hygiene guidelines. Participants had CBT-I in 30–60-minute individual, in-person sessions during weeks 1, 2, and 4; and had 15–30-minute phone sessions during weeks 3, 5, and 7. Study medicine was taken for 47 days from 7 am to 9 am and 12 pm to 2 pm.

Sample Characteristics

  • N = 88  
  • MEAN AGE = 56 years 
  • MALES: 12%, FEMALES: 88%
  • KEY DISEASE CHARACTERISTICS: Patients with any cancer who completed chemotherapy and/or radiation not less than one month prior and had no measurable disease
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients discontinued any prescribed or OTC sleep medications one week prior to the study and for the duration of the study

Setting

  • SITE: Not stated/unknown    
  • SETTING TYPE: Not specified  
  • LOCATION: United States and Canada

Phase of Care and Clinical Applications

  • PHASE OF CARE: Transition phase after active treatment

Study Design

  • Four am factorial
  • Randomized and blinded trials for medications but not for CBT-I

Measurement Instruments/Methods

  • Quantitative data of fatigue assessment using brief fatigue inventory (BFT)
  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale

Results

Improvement in fatigue was noted with CBT for insomnia (p = 0.002 on BFI;  p < 0.001 on FACIT-F). No improvement in fatigue was noted with placebo, on armodafinil alone, or on armodafinil with CBT-I.

Conclusions

CBT for insomnia appears to improve fatigue in patients with insomnia, and armodafinil was not shown to improve fatigue in patients with insomnia and fatigue.

Limitations

  • Small sample (less than 100)
  • Study was a secondary aim of a previous trial.

Nursing Implications

This study shows that CBT for insomnia may be beneficial to patients with fatigue and that armodafinil does not improve fatigue.

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Roscoe, J.A., Garland, S.N., Heckler, C.E., Perlis, M.L., Peoples, A.R., Shayne, M., . . . Morrow, G.R. (2015). Randomized placebo-controlled trial of cognitive behavioral therapy and armodafinil for insomnia after cancer treatment. Journal of Clinical Oncology, 33, 165–171.

Study Purpose

To evaluate whether cognitive behavioral therapy for insomnia (CBT-I) in combination with a wakefulness-promoting agent, armodafinil, results in better insomnia outcomes in cancer survivors compared to CBTI-I alone

Intervention Characteristics/Basic Study Process

Interventions used in this study included CBT-I and armodafinil. Seven standard CBT-I sessions following a published treatment manual were delivered in person (days 1, 2, and 4 for a duration of 30–60 minutes) and via telephone (days 3, 5, and 6 for a duration of 15–30 minutes). Participants began with a 50 mg dose of a single-isomer formulation of modafinil (armodafinil) given between 7 and 9 a.m. with a placebo given between 12 and 2 p.m. After three days, armodafinil was given in the morning and afternoon for 40 days followed by four days of twice-per-day armodafinil at 50 mg. All participants received sleep hygiene guidelines at the time of consent. Computer-generated randomization assigned participants to one of four groups: CBT-I, armodafinil, CBT-I plus armodafinil, or neither. All participants who did not receive armodafinil were given a placebo.

Sample Characteristics

  • N = 73  
  • MEAN AGE = 56 years
  • MALES: 12.5%, FEMALES: 87.5%
  • KEY DISEASE CHARACTERISTICS: Self-reported insomnia for at least three months that was caused or worsened by any cancer and its treatment; chemotherapy or radiation therapy completed greater than one month prior and no measurable disease; no sleep aids one week before baseline and throughout 11-week study
  • OTHER KEY SAMPLE CHARACTERISTICS: 68% breast cancer; original protocol called for only breast cancer but was broadened to include any cancers

Setting

  • SITE: Multi-site    
  • SETTING TYPE: Outpatient  
  • LOCATION: Two northeastern cities in the United States

Phase of Care and Clinical Applications

  • PHASE OF CARE: Late effects, survivorship

Study Design

Randomized, placebo-controlled trial

Measurement Instruments/Methods

  • Insomnia Severity Index (ISI)
  • Pittsburgh Sleep Quality Index (PSQI)
  • Demographics, clinical information, and sleep history

Results

Analyses controlling for baseline differences showed that both the CBT-I plus armodafinil (p = 0.001) and CBT-I plus placebo (p = 0.010) groups experienced significantly greater reductions in insomnia severity postintervention than the placebo group with effect sizes of 1.31 and 1.02, respectively. Similar improvements were seen for sleep quality. Gains on both measures persisted three months later. CBT-I plus armodafinil was not significantly different from CBT-I plus a placebo (p = 0.421), and armodafinil alone was not significantly different from a placebo alone (p = 0.584).

Conclusions

CBT-I results in significant and durable improvements in insomnia and sleep quality. Armodafinil did not significantly improve the efficacy of CBT-I or independently affect insomnia or sleep quality.

Limitations

  • Small sample (< 100)
  • Baseline sample/group differences of import
  • Questionable protocol fidelity
  • Subject withdrawals ≥ 10%
  • Other limitations/explanation: Patients were told of their random assignment to CBT-I (or another group) after the completion of the two-week baseline period. All study personnel and patients were blinded to medications (armodafinil or the placebo) but not to CBT-I assignment.

 

Nursing Implications

Considering the prevalence of insomnia in patients with cancer and survivors, the potential for poorer outcomes if insomnia remains untreated, and the efficacy of CBT-I in treating chronic insomnia, it is desirable that providers and patients obtain increased access to evidence-based nonpharmacologic sleep interventions as an integral part of comprehensive cancer care. The findings of this study demonstrated that the addition of armodafinil to CBT-I treatment did not improve results for sleep.

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