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

Сравнительный анализ атомоксетина и метилфенидата при СДВГ

Background
Psychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Direct comparison of efficacy is now possible due to availability of results from several head-to-head trials of these two medications.
Methods
All published, randomized, open label or double blind trials, comparing efficacy of methylphenidate with atomoxetine, in treatment of ADHD in children, diagnosed using DSM-IVTM criteria were included. The outcome studied was ADHDRS-IVParent:Inv score. The standardized mean difference (SMD) was used as a measure of effect size.
Results
Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included. Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD= 0.09, 95% CI -0.08-0.26) (Z=1.06, p=0.29). Synthesis of data from eight trials found no significant difference in response rates (RR=0.93 95% CI 0.76-1.14, p=0.49). Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD=0.32, 95% CI 0.12-0.53 (Z=3.05, p<0.002). Immediate release methylphenidate was not superior to atomoxetine (SMD= -0.04, 95% CI -0.19-0.12) (Z=0.46, p=0.64). Excluding open label trials did not significantly alter the effect size (SMD=0.08, 95% CI -0.04-0.21) (Z=1.27, p=0.20). All-cause discontinuation was used as a measure of acceptability. There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71). There was significant heterogeneity among the studies (p=0.002, I2=67%). Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p=0.001, I2=81%).
Conclusions
In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents. However OROS methylphenidate is more effective than atomoxetine and may be considered as first line treatment in treatment of ADHD in children and adolescents.

Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis

Женьшень и когнитивные функции

There is a lack of convincing evidence to show a cognitive-enhancing effect of Panax ginseng in healthy people and no high-quality evidence about its efficacy in patients with dementia, according to a report published online December 8 in the Cochrane Database of Systematic Reviews.

"Ginseng appeared to have some beneficial effects on cognition, behavior, and quality of life. However, at present, recommendations of continuing taking or stopping cannot be made due to lack of high-quality evidence," first study author JinSong Geng, of the Evidence-based Medicine Center, Medical School of Nantong University in Jiangsu, China, told Medscape Medical News.

Evidence That Ginseng Boosts Brain Function 'Not Convincing'

PHQ-9

Table 3. PHQ-9

1. Over the past 2 weeks, how often have you been bothered by any of the following problems?
	Not at all (0)	Several days (1)	More than half the days (2)	Nearly every day (3)
a. Little interest or pleasure in doing things
b. Feeling down, depressed, or hopeless
c. Trouble falling/staying asleep, sleeping too much
d. Feeling tired or having little energy
e. Poor appetite or overeating
f. Feeling bad about yourself -- or that you are a failure or have let yourself or your family down
g. Trouble concentrating on things, such as reading the newspaper or watching television
h. Moving or speaking so slowly that other people could have noticed. Or the opposite -- being so fidgety or restless that you have been moving around a lot more than usual
i. Thoughts that you would be better off dead or of hurting yourself in some way
2. If you checked off any problem on this questionnaire so far, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?
	Not difficult at all	Somewhat difficult	Very difficult	Extremely difficult

Table 4. Interpretation of PHQ-9 Results

Score/ Symptom Level	Treatment
0-4 No depression	Consider other diagnoses
5-9 Minimal	▪ Consider other diagnoses ▪ If diagnosis is depression, watchful waiting is appropriate initial management
10-14 Mild	▪ Consider watchful waiting ▪ If active treatment is needed, medication or psychotherapy is equally effective; consider function score in choosing treatment
15-19 Moderate	▪ Active treatment with medication or psychotherapy is recommended ▪ Medication or psychotherapy is equally effective
20-27 Severe	▪ Medication treatment is recommended ▪For many people, psychotherapy is useful as an additional treatment ▪ People with severe symptoms often benefit from consultation with a psychiatrist

Data from Kroenke K, Spitzer R. Psychiatr Ann. 2002;32:509-521.

A number of combinations have some benefit in selected patients, including:

• Lithium augmentation at stage 3 of STAR*D resulted in remissions in 15.9%.^[84] Lithium in combination with SSRIs and TCAs also has been effective in placebo-controlled studies, most involving small numbers of subjects. Such treatment requires monitoring of lithium levels, because there is a small difference between therapeutic and toxic levels.^[85]
• Thyroid hormone, and particularly triiodothyronine, has been studied for augmentation with the TCAs. In the STAR*D study, at step 3, augmentation with triiodothyronine led to a remission rate of 24.7%.^[84] Placebo-controlled studies have involved small numbers of subjects and have had mixed results.^[86]
• A heterocyclic-SSRI combination in 1 small study produced more rapid treatment onset and increased the likelihood of remission.^[87] In the study, a combination of fluoxetine and desipramine (a norepinephrine reuptake inhibitor) was more effective in achieving remission than either drug used as monotherapy: 53.8% for the combination, compared with 7.1% and 0%, respectively. However, such combinations can produce the serotonin syndrome, which is potentially life-threatening, and the dose of the heterocyclic must be adjusted using blood levels because SSRIs increase TCA levels through CYP-450 isoenzyme interactions (eg, fluoxetine increases the levels of desipramine 3- to 4-fold).^[88] Consequently, this augmentation strategy should rarely be considered in primary care.
• Mirtazapine has recently been evaluated in combination therapy with an SSRI (fluoxetine), an SNRI (venlafaxine), or bupropion.^[89] The investigators found that all 3 combinations were more effective than fluoxetine alone in achieving remission (52%, 58%, 46%, respectively, compared with 25%). In patients who responded, double-blind discontinuation resulted in relapse in about 40%. Of note, treatment was initiated with these combinations, rather than mirtazapine being used as an augmenting agent in those not initially responding.
• Methylfolate and folate have been used to augment SSRIs, resulting in increased rates of remission, particularly in women.^[90] The degree to which the response is due to folate deficiency, and whether methylfolate is of greater benefit due to its increased ability to cross the blood-brain barrier, are subject to further research.
• Antidepressants and hypnotics have been used together, with early improvement not only in sleep measures, but also in rates of depression remission.^[91]
• Stimulant drugs have been used as augmentation of heterocyclics or SSRIs.^[92] Of note, in individuals with comorbid medical illness, amphetamine stimulants should be used with caution, particularly if cardiac disease is potentially present.

Clinical and Pharmacologic Strategies to Achieve Remission in Depression

Психические расстройства при злоупотреблении кофеином

Causes

* The means by which caffeine exerts its pharmacologic effects remains a subject of active research.
* A leading theory suggests that caffeine is an adenosine receptor antagonist that blocks 2 major types of adenosine receptors, A1AR and A2AAR.9
* Adenosine is an inhibitory neuromodulator affecting norepinephrine, dopamine, and serotonin activity.
* Caffeine's putative antagonism of adenosine would increase those neurotransmitters promoting psychostimulation.
* The same neurotransmitter systems are implicated in the pathophysiology of several psychiatric disorders.

Caffeine-Related Psychiatric Disorders

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?

Винпоцетин при деменции

All identified studies were performed before the 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30mg/day and 60 mg/day compared with placebo, but the number of patients treated for 6 months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials. REVIEWER'S CONCLUSIONS: Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.

Vinpocetine for cognitive impairment and dementia.

Психотическая симптоматика после злоупотребления энергетическими напитками у больного шизофренией

Caffeine functions in the central nervous system as a competitive antagonist of adenosine receptors, A1 and A2A, and alters neurotransmitter release, including dopamine and glutamate. This dopamine release in the striatum may underlie caffeine's reinforcing properties, and the modulation of the mesolimbic dopamine pathway may be related to its psychotomimetic effect (1). Exaggerated effects may be seen in patients with schizophrenia using high-dose caffeine (2). The energy drink the patient in the present case consumed contained 160 mg of caffeine per can. The patient weighed 67 kg and therefore consumed approximately 20 mg/kg per day of caffeine. Psychosis has been reported at doses near 10 mg/kg per day (3), which is well below the known toxic dosage (150–200 mg/kg) but above the average intake by the numerous schizophrenia outpatients who use caffeine (1.8–4.1 mg/kg per day [depending on smoking status]) (4).

Psychosis Following Excessive Ingestion of Energy Drinks in a Patient With Schizophrenia

Treatment of Catatonia With Methylphenidate in an Elderly Patient With Depression

Matthew L. Prowler, M.D., David Weiss, M.D., and Stanley N. Caroff, M.D.

Received June 2, 2008; revised July 1, 2008; accepted July 2, 2008. From the Dept. of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA; and the Philadelphia Veterans Affairs Medical Center. Send correspondence and reprint requests to Matthew L. Prowler, M.D., Dept. of Psychiatry, University of Pennsylvania School of Medicine, 3535 Market St., 2nd Fl., Philadelphia, PA 19104. e-mail: matthew.prowler@uphs.upenn.edu
© 2010 The Academy of Psychosomatic Medicine

BACKGROUND: Catatonia is especially common among patients with mood disorders. OBJECTIVE: The authors evaluated the effects of methylphenidate as an augmentation strategy in an elderly patient with catatonia and depression. METHOD: Methylphenidate was administered to a catatonic patient who had not responded to lorazepam. RESULTS: The patient showed an acute and marked response to methylphenidate. DISCUSSION: Methylphenidate may be effective as an adjunct in elderly depression patients with catatonia, as well as in medically ill, apathetic patients. However, there have been few attempts to study the role of psychostimulants in alleviating catatonia in general, or catatonia associated specifically with an underlying depressive disorder, even though catatonia is frequently associated with mood disorders.

Treatment of Catatonia With Methylphenidate in an Elderly Patient With Depression