Особенности воздействия пароксетина тревожную и депрессивную симптоматику

This is rather remarkable. Everyone calls paroxetine "an antidepressant", yet at least in one important sense it works better against OCD and social anxiety than it does against depression!

In fact, is paroxetine an antidepressant at all? It works better on MADRS and very poorly on the HAMD; is this because the HAMD is a better scale of depression, and the MADRS actually measures anxiety or OCD symptoms?

That's a lovely neat theory... but in fact the HAMD-17 has two questions about anxiety, scoring 0-4 points each, so you can score up to 8 (or 12 if you count "hypochondriasis", which is basically health anxiety, so you probably should), out of a total maximum of 52. The MADRS has one anxiety item with a max score of 6 on a total of 60. So the HAMD is more "anxious" than the MADRS.

This is more than just a curiosity. Paroxetine's antidepressant effect was tiny in those aged 25 or under on the HAMD - treatment just 9% of the placebo effect - but on the MADRS in the same age group, the benefit was 35%! So what is the HAMD measuring and why is it different to the MADRS?

Honestly, it's hard to tell because the Hamilton scale is so messy. It measures depression and the other distressing symptoms which commonly go along with it. The idea, I think, was that it was meant to be a scale of the patient's overall clinical severity - how seriously they were suffering - rather than a measure of depression per se.

Paxil: The Whole Truth?

Эндоканнабиноиды и бег

Recent findings show that exercise increases serum
concentrations of endocannabinoids, a result suggestive of a
new possible explanation for a number of these changes.
Further research is necessary to characterise the precise
nature of this endocannabinoid response to exercise, speci-
fically the relative importance of factors such as the nature of
the activity, exercise duration, exercise intensity, sex, and
age. In addition, animal models can be used to identify the
production and binding sites of endocannabinoids as well as
their functional role in exercise.
The cannabinoids produce psychological states that closely
parallel several experiences described as being related to the
runner’s high. Compared with the opioid analgesics, the
analgesia produced by the endocannabinoid system is more
consistent with exercise induced analgesia. Activation of the
endocannabinoid system also produces sedation, anxiolysis, a
sense of wellbeing, reduced attentional capacity, impaired
working memory ability, and difficulty in time estimation.
This behavioural profile is similar to the psychological
experiences reported by long distance runners. Considerable
research is needed to clarify to what extent the endocanna-
binoid system might be responsible for the exercise induced
changes in mental status. Nevertheless, a significant upre-
gulation of serum concentrations of endocannabinoids has
recently been reported in endurance athletes, and studies are
underway to explore this further in laboratory animals.
The close interaction of endocannabinoids with dopamine
shows that they have a function in the brain’s reward system
and therefore possibly addiction. The endocannabinoid
system is also implicated in the control of motor activity
mediated through the basal ganglia, and central activation of
anandamide in freely moving rats has been demonstrated.
Finally, the endocannabinoid system mediates peripheral
effects such as vasodilation and bronchodilation that may
play a contributory role in the body’s response to exercise.

Endocannabinoids and exercise

Significant Weight Gain Associated with Post-Clozapine Antipsychotics

Significant Weight Gain* Associated with Post-Clozapine Antipsychotics
*≥7% body weight increase vs placebo; 4-8 week trials

Пролонгированная инъекционная форма рисперидона вызывает больше побочных эффектов

Long-acting, injectable risperidone, the first second-generation antipsychotic available in the United States in this formulation, is no better than oral antipsychotics for the treatment of unstable schizophrenia, a new study published in the March 3 issue of the New England Journal of Medicine suggests.

In a randomized study of more than 300 Veterans Affairs (VA) patients, investigators found injectable risperidone did not significantly decrease hospitalization rates or improve symptoms, social function, or quality of life compared with those treated with "clinicians' choice" of oral antipsychotics. The risperidone-treated group also reported more adverse effects.

No Benefit, More Side Effects With Injectable Risperidone

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

Механизмы действия новейших антипсихотиков

Early pharmacotherapeutic agents used for schizophrenia targeted neuronal pathways related to psychosis. One of the first pharmacologic agents used in the treatment of patients with schizophrenia was the antihypertensive agent reserpine. The antipsychotic effects of this drug result from reduction of synaptic dopamine release.

For those who believe that focusing on these variations in neuropharmacologic binding effects is of minor importance, recall that the first effective antiobsessive, the tricyclic antidepressant chlomipramine, differs from imipramine by only 1 chloride atom substitution.31 It was hard to believe that chlomipramine would be effective for obsessive-compulsive disorder (OCD) when imipramine was not, but that is, in fact, what happened.

Iloperidone is an antipsychotic that was approved in May 2009 for the acute treatment of schizophrenia in adults. The mechanism of action, which involves antagonism of serotonin-2A (5HT-2A) and dopamine 2 receptors with a high 5HT-2A/D2 ratio, is similar to other atypical antipsychotics. Its efficacy appears to be similar to haloperidol, risperidone, and ziprasidone. It also has a very low EPS and akathisia profile, for reasons that are not well understood. It has strong alpha-adrenergic antagonism effects, and therefore requires a cautious dosing and titration schedule to reduce the potential for orthostatic hypotension and dizziness. The lack of affinity of iloperidone for other receptors (e.g., histamine, muscarinic) results in a low antihistaminic and anticholinergic side effect profile.37

Asenapine, approved for acute and maintenance treatment of schizophrenia, has a unique human receptor signature with binding affinities and antagonistic properties that are substantially different from other available schizophrenia treatments. Asenapine, which is administered sublingually, is a potent antagonist at several serotonin receptors38 and also has high affinity for alpha-adrenergic and dopaminergic receptors, which suggests potential for both antipsychotic and cognitive-enhancing properties.39 Clinical trial data demonstrate strong efficacy for positive symptoms, and there is some evidence of beneficial effects on negative and cognitive symptoms.

Expanding the Treatment Paradigm in Patients With Schizophrenia: Beyond Psychotic Symptoms

Стратегии лечения тиков при синдроме Туретта

The majority of treatment options for tics are pharmacological. The most commonly prescribed drugs are primarily dopamine antagonists, such as neuroleptics (e.g. haloperidol), benzamides (e.g. sulpiride) or atypical antipsychotics (e.g. risperidone). Other agents that may be efficacious include drugs which modulate noradrenaline (e.g. clonidine), GABA (e.g. benzodiazepines) and acetylcholine (e.g. nicotine). Nonpharmacological interventions include behavioural approaches such as habit reversal training and exposure response prevention therapy. Surgical techniques involving deep brain stimulation (DBS) of the thalamus or globus pallidus may also be considered for severe, treatment refractory patients. Some of the more recent treatments that have been trialled include electroconvulsive therapy and repetitive transcranial magnetic stimulation.

.
Treatment Strategies for Tics in Tourette Syndrome

Оксибутинин в качестве корректора гипергидроза вызванного приёмом антидепрессантов

Patient A is a 59-year-old man with a history of recurrent episodes of panic disorder, for which he had used paroxetine, venlafaxine, and escitalopram as well as high doses of oxazepam in the past. He was admitted to the hospital because of a severe depressive episode with suicidal ideation. The depression was successfully treated with clomipramine, 100 mg/day, which was effective for the treatment of panic attacks as well. Although he sweated all over his body, he was willing to continue clomipramine monotherapy after discharge. Lowering the dosage did not change the situation, nor did treatment with cognitive-behavioral therapy. Finally, a trial with oxybutynin, 2.5 mg b.i.d., relieved the hyperhidrosis completely, without any side effects.

Patient B is a 60-year-old man with recurrent severe depressive episodes with psychotic symptoms and agitation. Typical for his disorder are the rapid onset of relapse and the severity of agitation, which in the past required hospitalization and seclusion. In the latest episode he was treated with clomipramine, 75 mg/day, and olanzapine, 15 mg/day, but he suffered from severe hyperhidrosis. A switch from olanzapine to haloperidol did not change the hyperhidrosis. Later, 800 mg/day of lithium was successfully added for the treatment of his depressive symptoms. Oxybutynin, 5 mg t.i.d., was added to his treatment and relieved his hyperhidrosis without side effects.

There are several preferential strategies to treat hyperhidrosis, such as lowering the dosage or altering the dosing schedule, changing clothing or food habits, or regulating anxiety (2). In the present two cases, these strategies were unsuccessful and oxybutynin maintenance treatment was introduced. With its rapid, short-term effect (within an hour), oxybutynin could also be considered "as needed" in specific social situations. One should be careful in dosing to avoid anticholinergic side effects such as constipation, urinary retention, and blurred vision. Although placebo-controlled research is necessary, the cases reported here suggest that adding oxybutynin to antidepressants can be a simple and effective treatment option for hyperhidrosis.

Oxybutynin for Antidepressant-Induced Hyperhidrosis

Ацетилцистеин в психиатрической практике

Through its metabolic contribution to glutathione production, cysteine participates in the general antioxidant activities of the body. Through its role as a modulator of the glutamatergic system, cysteine influences the reward-reinforcement pathway. Because of these functions, NAC may exert a therapeutic effect on psychiatric disorders allegedly related to oxidative stress (e.g., schizophrenia, bipolar disorder) as well as psychiatric syndromes characterized by impulsive/compulsive symptoms (e.g., trichotillomania, pathological nail biting, gambling, substance misuse). While the dosages, pharmacological strategies (monotherapy versus augmentation), and long-term risks are not fully evident, NAC appears to be a promising, relatively low-risk intervention.

Getting a Knack for NAC

Риск обострения при отмене препаратов через год после первого эпизода и при противорецедивной терапии кветиапином

Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.

Interventions Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.

Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.

Results 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; χ2=3.20, df=1; P=0.07).

Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year.

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Случай ухудшения маниакальной симптоматики при приёме низких доз кветиапина

The mechanism of antidepressant action of quetiapine is unclear. However, it has been suggested that its antidepressant activity is mediated by its metabolite N-Desalkylquetiapine, which leads to norepinephrine reuptake transporter inhibition and partial serotonin 1A agonism.4 A speculation may be that slow clearance of the metabolites as an age effect or genetic trait in this case led to very high levels of N-Desalkylquetiapine potentiating quetiapine's antidepressant effect and leading to worsening of mania. Moreover, a positron emission tomography (PET) study using quetiapine 750 mg or 450 mg/day found that there was no D2 receptor occupancy at the low dose of quetiapine, while 5HT2A receptor occupancy was consistently high.5 Despite the normal head CT scan, brain-aging related neurotransmitter changes and therefore different medication effects could be considered. Calabrese et al.1 reported an incidence of treatment-emergent mania 2.2% with 600 mg/day of quetiapine and 3.9% with 300 mg/day of quetiapine. The absence of dopaminergic receptors blockade and the high affinity for serotonergic receptors at lower doses, may explain quetiapine's antidepressant activity and worsening mania in case of slow titration in manic patients. In this case, geriatrician treatment practice of "start low and go slow" raised questions.

Worsening Mania Associated With Slow Increase of Quetiapine Dose

Перерыв в лечении ГТР венлафаксином не осложняет достижения ремиссии

After study procedures were completed, the researchers offered venlafaxine XR for six months to the subjects who had relapsed after being switched from venalfaxine treatment to a placebo. Twenty-seven subjects accepted the offer. Preliminary results indicated that they again improved to the same degree as patients who had been on it for 12 months. “These results surprised us,” Rickels said. “If this finding can be repeated, it would mean that patients who are for at least six months on venlafaxine XR could go off medication until the symptoms return.”

Extended GAD Treatment Keeps Relapse Rates Low

Влияние возраста приёма терапии эстрогеном на когнитивное снижение пожилом возрасте

Specifically, taking estrogen around the time of menopause is linked to a lowered risk of dementia for women as they enter old age, but estrogen therapy in late life is associated with a higher risk for dementia, according to a retrospective study led by Dr. Kristine Yaffe, chief of geriatric psychiatry at the San Francisco VA Medical Center.

Age During Estrogen Therapy May Impact Later Dementia

Сезонное аффективное расстройство в рамках БАР и рекуррентной депрессии

Many see seasonal affective disorder (SAD) as synonymous with winter depression. However, depression is only half of the problem; spring and summer mania tend to be ignored. Beginning with winter depression, core symptoms resemble hibernation. People sleep more, eat more, and are less interested in usual activities. They are not sad in mood, typically, and may be unaware that their slowed down, uninterested behavior reflects a kind of depression.

Moreover, light itself is not the only cause of depression. Light interacts with a person's own sensitivity to depression. Some people, especially those with bipolar disorder or recurrent unipolar depression, are sensitive to changes in light, and will develop winter depression even in areas with reasonable light levels, such as Georgia or Italy. Others are insensitive to light, and will not develop SAD even in areas with low light levels, such as New England or Scandinavia.

This leads to another misconception about SAD. It is a diagnosis of exclusion, and should not be diagnosed in persons with bipolar disorder or recurrent unipolar depression. SAD means someone has only depression in the winter, and almost never has depression any other time of year.

Light entrains our circadian rhythms; it is what keeps us on regular sleep-wake cycles. When sleep is impaired and reduced, an antidepressant effect occurs, and, in sensitive persons, mania materializes. This is what takes place in the spring and summer when light greatly increases. Longer duration of sleep leads to depression in sensitive persons. Circadian cycles appear to be biologically abnormal in people with bipolar disorder and recurrent depression, hence their sensitivity to light. One of the effects of lithium, for instance, is to lengthen circadian cycles, which appear to be abnormally shortened in animal models of mania.

I've developed my own recommendations for both winter depression and summer mania, which one could call "light precautions." They are as follows, briefly.

In winter. Increase your exposure to light as much as possible. Go out for a walk at noon for up to an hour without any sunglasses on; sleep with all the blinds up.

In summer. Reduce your exposure to light as much as possible: Always wear sunglasses; get room-darkening shades; and sleep in as much darkness as possible. (It is key to adjust one's exposure to natural morning sunlight. It is amazing how many people who oversleep never think of pulling up their window shades, and how many people who don't sleep enough don't think about getting room-darkening window shades.)
Light Box Treatment

Light box treatment essentially replaces the sunlight that is missing in wintertime. Most light boxes provide about 10,000 lux of light, and are meant to be used in the mornings, which is when the sun would normally have risen earlier than it does in the depths of winter. Patients should read or eat breakfast while exposed to indirect light from the box at about arm's length for about 30 minutes daily. Just as one does not directly look at the sun, patients should not directly look at light boxes; this causes ocular damage.

The Truth About Seasonal Affective Disorder

Клинические разборы случая аутоперсонамнезии (аутобиографической амнезии)

Все же в его случае адекватнее говорить не об аутоперсонамнезии, а об аутоперсонагнозии, как синониме семантической агнозии на лица (просоп-агнозии), даже более адекватном, так как речь идет не только о лицах, а о сфере «приватного». Стоит напомнить, что термин «агнозия» был введен Зигмундом Фрейдом (1891), в тот период крупным невропатологом, вместо термина «асимболия», в силу нарушения связи не предмета с его знаком (символом), а знака и смысла. Таким образом, зрительное восприятие сохранено, но смысл предмета непонятен. Отсюда старый термин «душевная слепота». Что касается семантической просопагнозии, то это расстройство не восприятия, и не столько памяти, сколько самосознания.

Случай аутоперсонамнезии. Диагностический разброд – подарок антипсихиатрам