Метаболические расстройства коморбидные с БАР

Chronic stress, which patients experience during both the manic and the depressive phases of bipolar disorder, is associated with increased cortisol levels, lack of cortisol suppression, and changes in hypothalamic-pituitary-adrenal axis responses. This metabolic dysregulation may increase insulin resistance and can lead to hyperglycemia, increased oxidative stress, metabolic syndrome, and atherosclerosis. In addition, patients with bipolar illness have increased activity of the sympathetic nervous system, which may also lead to insulin resistance, metabolic syndrome, and increased risk of sudden cardiac death.2

Depressive syndromes may be neurotoxic. Abnormalities in cellular plasticity, cellular resilience, and intracellular signaling, as well as alterations in the size, shape, and density of neurons and glia, have been found. Studies employing neuroimaging and neuropsychological tests have demonstrated abnormalities in brain morphology and function in patient populations with depressive syndromes and in those with diabetes. Common physiologic mechanisms have been implicated, including insulin-glucose homeostasis, immuno-inflammatory processes, and oxidative stress mechanisms.


Metabolic Comorbidities in Patients With Bipolar Disorder

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

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

Азенапин

A new antipsychotic drug, asenapine, has been approved by the Food and Drug Administration (FDA) for the acute treatment of schizophrenia and manic or mixed episode in bipolar I disorder in adults.

Similar to other second-generation antipsychotics, asenapine is an antagonist of the serotonin 5HT2 and dopamine D2 receptors.

In the long-term schizophrenia trial, three of the 908 patients (0.3 percent) treated with asenapine had a QTc interval increase from baseline of greater than 60 msec. None had a QTc interval increase of 500 msec or more.

Asenapine is formulated as sublingual tablets to optimize its bioavailability upon absorption, since the drug is extensively metabolized in the liver. The tablet should not be swallowed. The approved dosage for acute schizophrenia treatment is 5 mg twice daily. The dosage for bipolar I disorder is to start with 10 mg twice daily with the option of decreasing to 5 mg twice daily if the patient experiences adverse effects.

Asenapine Adds to Arsenal to Treat Psychotic Disorders

Newer Treatments for Schizophrenia May Offer New Benefits and Drawbacks

The benefit of this therapy is that physicians can determine who may best respond. Studies have identified 6 genetic markers that are associated with iloperidone effectiveness and safety. Patients with 0 to 2 markers have approximately a 15% clinical response to iloperidone treatment. Those with 3 markers have approximately a 40% likelihood of improvement, and those with 4 markersare approximately 60% likely to improve. Almost all patients with 5 or 6 markers were shown to respond to treatment. “Even if you don’t know anything about a patient, there is still about a 48% chance of a clinical response to treatment, according to Potkin.
Newer Treatments for Schizophrenia May Offer New Benefits and Drawbacks

Long-term findings for the novel antipsychotic agent asenapine did not confirm any advantage over second-generation antipsychotics for negative symptoms of schizophrenia...Extrapyramidal symptoms were "slightly" higher at 10.4% with asenapine compared with 4.1% with olanzapine. Prolactin, hepatic enzymes, lipids, glucose, and the QTC interval were similar or better with asenapine.
New Drug No Better for Negative Schizophrenia Symptoms