Table 2.
Medications commonly used in the treatment of MS with the potential to disrupt sleep and proposed adaptations to avoid or decrease sleep disruption.
| Medication | Indication in MS | Effects on sleep | PSG data | Proposed MoA | Adaptation |
|---|---|---|---|---|---|
| DMTs | |||||
| Interferon-beta | First-line DMT | Fatigue, hypersomnolence, insomnia | Reduction of sleep efficiency | Reduces antigen presentation and T-cell proliferation; alters cytokine expression | Switch from evening to morning injection |
| Glatiramer acetate | First-line DMT | More frequent awakenings and daytime somnolence; increased anxiety and irritability | Not available | Partly due to increase in anti-inflammatory cytokines (IL-4 and IL-10) through activation of the Th-2 cell pathway of immunity | |
| Natalizumab | Second-line DMT | Improvement in fatigue, daytime sleepiness and depression | Not available | Monoclonal antibody against the α-4 subunit of α-4 β-1 integrin that inhibits the ability of activated T cells to migrate across the blood–brain barrier into the CNS | |
| Symptomatic medications | |||||
| Methylprednisolone | Acute relapse | Insomnia | Decreased REM sleep | Decreased cytokine cascade, activation of B and T cells and ability of immune cells to penetrate the CNS | Lifestyle changes, CBT, pharmacological intervention (if needed) |
| Modafinil | Fatigue | Insomnia | Reduced sleep latency | Unknown | |
| Methylphenidate | Fatigue | Insomnia | REM sleep suppression | Increased catecholamine release and reuptake inhibition | |
| Amantadine | Fatigue | Insomnia | Not available | Presynaptic dopamine release | |
| Pemoline | Fatigue | Not available | CNS stimulant | ||
| 4-Aminopyridine | Fatigue | Insomnia | Not available | Block of K channels in neurons | |
| Baclofen | Spasticity | Sedation | Total sleep time increased and reduced wake after sleep onset | GABA-B receptor agonist | |
| Clonazepam | Spasticity, anxiety | Somnolence | Increased total sleep time, reduced sleep latency and wake after sleep onset, increased spindle activity and reduced REM sleep | GABA-A receptor agonist | |
| Tizanidine | Spasticity | Daytime drowsiness | Improvement in sleep induction and maintenance | Central α-2 adrenoreceptor agonist | |
| SSRI | Depression, anxiety | Insomnia or sedation | Decreased total sleep time, increased stage 1 sleep, decreased REM sleep, increased sleep latency, “Prozac eyes” and periodic limb movements | Inhibition of serotonin reuptake | |
| Gabapentin | Pain seizures | Sleepiness | Decreased sleep stage 1, increased sleep stage 3, reduced periodic limb movements, increased REM sleep | May promote formation of GABA in the CNS | |
| Oxybutynin | Urinary frequency | Sedation | Decreased REM sleep and increased REM sleep latency | Anticholinergic agent | |
| Cannabis-based medicinal extracts | Spasticity, bladder dysfunction, central neuropathic pain | Improved sleeping difficulty and sleep quality, diminished awakenings and sleepiness | Not available | Inhibition of smooth muscle contraction, interaction with the cholinergic receptor system and/or synergism with anticholinergic medication, analgesic properties | |
Adapted from Brass et al. (47) and Lanza et al. (48). CBT, cognitive behavioural therapy; CNS, central nervous system; DMT, disease-modifying therapy; GABA, gamma-amino-butyric acid; IL, interleukin; K, potassium; MoA, mechanism of action; MS, multiple sclerosis; PSG, polysomnography; REM, rapid eye movement; SSRI, selective serotonin reuptake inhibitor.