Психостимуляторы для пожилых больных

Psychostimulants are recognized for their role in managing attention-deficit/hyperactivity disorder
(ADHD), but also have found a treatment niche in conditions such as apathy, fatigue, and depression.

Psychostimulants for older adult

Фармакотерапия когнитивных нарушений при травмах головного мозга

Recommended treatments for mild TBI-related cognitive deficits

Deficit	First-line medication	Side effects	Contraindications	Other treatments
Memory	Donepezil (5 to 10 mg/d)	Diarrhea, nausea, vomiting, muscle cramps, fatigue, anorexia	Hypersensitivity to donepezil or piperidine derivatives	Rivastigmine, galantamine, physostigmine, CDP-choline
Speed of processing	Methylphenidate (0.3 mg/kg twice daily)	Headache, insomnia, decreased appetite, nausea, vomiting, anxiety, irritability	Hypersensitivity to methylphenidate, glaucoma, history of Tourette syndrome or tics, use of MAOI within 14 days	Dextroamphetamine
Executive function	Amantadine (200 to 400 mg/d)	CNS depression, orthostatic hypotension, peripheral edema, agitation, nausea, anorexia	Hypersensitivity to amantadine	Bromocriptine, pramipexole, carbidopa/levodopa
CDP-choline: cytidinediphosphocholine; MAOI: monoamine oxidase inhibitor
Source:Reference 8

Executive function responds to non-stimulant catecholaminergics. In a review, Writer and Schillerstrom5 found that TBI patients who received catecholaminergic augmentation showed improved function in 6 of 7 studies. In 2 randomized controlled trials (RCTs) and 4 nonrandomized, placebo-controlled trials, patients with mild to severe TBI showed improved executive function, attention, global cognitive function, memory, language, and/ or arousal with use of bromocriptine, pramipexole, carbidopa/levodopa, or amantadine.5 The greatest improvements were found in executive function. In 1 RCT, 10 patients with mild to severe TBI showed no functional improvement after 2 weeks of treatment.

Amantadine, 200 to 400 mg/d, has been shown to safely improve arousal and cognitive function in patients with moderate to severe TBI when started 3 days to 5 months after injury.9 Amantadine, 400 mg/d, also improves executive function measures without significant benefit in attention or memory in patients with mild to severe TBI 6 months post-injury.10

Memory responds to cholinesterase inhibitors. Memory deficits secondary to TBI affect immediate and delayed memory. The cholinesterase inhibitor donepezil is approved for treating Alzheimer’s disease (AD) in the United States and Canada, and research suggests memory deficits after TBI may be similar to those seen in AD.11 This includes deficits in long-term memory storage, which likely is associated with the cholinergic system.11 Post-mortem studies have found similarities in traumatically injured brains and those of AD patients.11

Three small prospective studies of done-pezil have shown improved memory and attention in TBI patients when cognition is the primary outcome, with 1 small negative open-label trial.7 In a study of 53 patients, Whelan et al12 found that donepezil improved patients’ intelligence quotient and clinician-based assessment of cognition over 2 years. Taverni et al13 found memory improvement in 2 TBI patients within 3 weeks of starting donepezil. These results suggest that donepezil may be used in acute and late phases of memory deficits following mild, moderate, or severe TBI.6 All studies titrated donepezil from 5 to 10 mg/d over several weeks. Dosing guidelines for donepezil in AD suggest 5 mg/d for 4 to 6 weeks, which may be increased to 10 mg/d if needed.8

Rivastigmine (3 to 6 mg/d) has been shown to be effective in mild TBI when started 1 year after injury and safe for 12 to 38 weeks of treatment.14,15 One retrospective cohort study of 111 patients with chronic TBI found no difference among donepezil, rivastigmine, or galantamine, with mean doses of 7.2 mg/d, 10 mg/d, and 2.3 mg/d, respectively.16 Sixty-one percent of patients showed improvement and the remainder had modest or no response. This study suggests that positive response on cognition may be similar among cholinesterase inhibitors. In case reports, physostigmine has offered some benefit17,18; however, cardiovascular and autonomic side effects restrict its use.11 Tacrine is associated with problematic gastrointestinal and hepatic side effects.

Processing speed responds to stimulant catecholaminergics. Although the incidence of psychiatric illness is not correlated with TBI severity, evidence suggests that speed of processing mediates the relationship between injury severity and functional decline.19 Therefore, aggressively treating these deficits may help improve function.

Methylphenidate improves attention and processing speed after TBI. A review of 7 randomized trials and 2 nonrandomized trials indicated that patients with mild to severe, chronic TBI experienced significantly improved cognitive function after methylphenidate treatment.5 Willmott and Ponsford20 found significant enhancement in information processing speed within 2 weeks of methylphenidate treatment in 40 patients with moderate or severe TBI. Methylphenidate increased the rate of recovery and led to improvement in acute21 and post-acute phases.22 In addition, methylphenidate may improve processing speed even in the absence of significant changes in attention.23

The standard methylphenidate dose used in most studies, 0.3 mg/kg twice daily, is safe and effective. Dosing usually is started at 5 mg/d and titrated to symptomatic relief. Because methylphenidate does not lower the seizure threshold, it is safe for patients at high risk for seizure.24 Methylphenidate also significantly improves attention and speed of processing in pediatric head trauma.25,26

Dextroamphetamine also is used to treat speed of processing dysfunction after TBI, but is less studied than methylphenidate. Dextroamphetamine, 5 to 30 mg/d, was found to effectively treat attention problems that interfered with rehabilitation in patients with severe TBI.

Traumatic brain injury: Pharmacotherapy options for cognitive deficits

Стимуляторы при БАР

Clinical studies of stimulant use in patients with bipolar disorder

Stimulant(s) studied	Study design	Patients studied	Clinical outcomes
Traditional stimulants
Adjunctive methylphenidate	Chart review, naturalistic	16 adults (5 with comorbid ADHD, 11 with bipolar depression)	Improvements in depression, overall functioning, and ability to concentrate; sleep disturbance, irritability/agitation reported
Adjunctive methylphenidate or racemic mixture of AMPH salts	Chart review of sedation and depressive symptoms	8 adults (BD II)	Improved clinical impression of bipolar illness; no manic switches, changes in cycling patterns, or substance abuse noted
Adjunctive methylphenidate	12-week open study, bipolar depression	12 adults (10 BD I, 2 BD II)	Significant clinical improvements in depressive symptoms; no change in manic symptoms; anxiety, agitation, and hypomania reported
Multiple stimulants	Chart review, history of stimulants and bipolar illness course	34 hospitalized adolescents	Prior stimulant treatment associated with earlier age of illness onset
Adjunctive mixed amphetamine salts	Randomized, placebo-controlled; comorbid BD and ADHD	30 children with ADHD symptoms stabilized on divalproex sodium	Decrease in ADHD symptoms with adjunctive amphetamine treatment but not with divalproex sodium alone; 1 case of mania
Novel stimulant
Adjunctive modafinil	Case series	Mixed sample of depressed adults (4 unipolar, 3 bipolar)	Significant improvement in depressive symptoms
Adjunctive modafinil	Randomized, double-blind, placebo-controlled	85 adults with bipolar depression	Treatment group showed greater response and remission of depressive symptoms compared with placebo group; no difference in development of manic symptoms
ADHD: attention-deficit/hyperactivity disorder; AMPH: amphetamine; BD: bipolar disorder; NOS: not otherwise specified

Adding a stimulant could improve residual symptoms, but it also might cause serious side effects, toxicities, and destabilization.

Stimulants for adult bipolar disorder?