Различия в действии антипсихотиков на обсессивно-компульсивную симптоматику при шизофрении

Indirect evidence supports the assumption that antiserotonergic second-generation antipsychotics (SGA) induce and aggravate obsessive–compulsive symptoms (OCS) in schizophrenia. However, multimodal studies assessing the long-term interaction of pharmacotherapy and psychopathology are missing. Over 12 months, we followed-up 75 schizophrenia patients who were classified into two groups according to antipsychotic treatment: clozapine or olanzapine (group I) versus aripiprazole or amisulpride (group II). We applied the Yale Brown Obsessive Compulsive Scale (YBOCS) and investigated between-group changes over time as the primary endpoint. Group I showed markedly higher YBOCS scores at both time points. Repeated measure analyses of variance (ANOVAs) revealed significant interaction effects of group and time (per protocol sample (PP): p=0.006). This was due to persistently high OCS severity within group I, and decreasing YBOCS scores within group II. OCS severity correlated significantly with the negative and general psychopathology subscales of the Positive and Negative Syndrome Scale (PANSS), as well as with depressive symptoms. The progressive differences in OCS severity between our groups support the assumption of differential pharmacodynamic effects on comorbid OCS in schizophrenia. Further studies should address the pathogenetic mechanism, define patients at risk and facilitate early detection as well as therapeutic interventions.

Differential effects of antipsychotic agents on obsessive–compulsive symptoms in schizophrenia: a longitudinal study

Изучение компульсивного поведения у собак

Researchers discovered a connection with stereotypic OCD behavior and vitamins and minerals. Dogs that received nutritional supplements, especially vitamins and minerals, with their food, chased their tails less.

“Our study does not prove an actual causal relationship between vitamins and lessened tail chasing, but interestingly similar preliminary results have been observed in human OCD,” said researcher Katriina Tiira, Ph.D.

 Study of Canine OCD May Help Humans

Амисульприд-индуцированная акатизия как маркер нарушения взаимоотношений серотонина и дофамина при ОКР

We report about a clinical observation in a well-characterized group of patients with obsessive–compulsive disorder (OCD) during an experimental medicine study in which a single dose of amisulpride (a selective D2/3 antagonist) was administered. Almost half of the OCD patients, in particular those with less severe obsessive–compulsive symptoms, experienced acute akathisia in response to the amisulpride challenge. This unexpectedly high incidence of akathisia in the selective serotonin reuptake inhibitor (SSRI)-treated patients with OCD suggests that individual differences in dopamine–serotonin interactions underlie the clinical heterogeneity of OCD, and may thus explain the insufficiency of SSRI monotherapy in those patients not experiencing a satisfactory outcome in symptom reduction. We further speculate about the neuropathology possibly underlying this clinical observation and outline a testable hypothesis for future molecular imaging studies.

 Amisulpride-induced acute akathisia in OCD: an example of dysfunctional dopamine–serotonin interactions?

Аутоиммунные факторы в патогенезе обсессивно-компульсивной симптоматики

Background
Symptoms of obsessive–compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis.
Aims
To test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults.
Method
Ninety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n = 33) and schizophrenia (n = 17).
Results
Positivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher’s exact test P = 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls.
Conclusions
These findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.

Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study

Blepharospasm as an Obsessive-Compulsive Phenomenon

Случай улучшения в обсессивно-компульсивной симптоматике после инсульта

Within weeks of her stroke, she realized that her obsessive and intrusive thoughts, fears, rituals, and impulsive behavior had completely resolved. In addition, there was some improvement in her temperament. There was no improvement in attention or concentration. Owing to her improvement in neuropsychiatric symptoms, she strongly felt that her stroke was beneficial. These benefits have persisted for 24 months.

A Stroke Of Good Fortune Cures OCD?

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?

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

Глутаматергические механизмы ОКР

Glutamatergic Dysfunction in Obsessive-Compulsive Disorder and the Potential Clinical Utility of Glutamate-Modulating Agents