Come the year 2012 there could be a new antidepressant with a novel mechanism of action on the market in these United States (1). As the drug is still in development, it is known as "TC-5214."
According the the press release, TC-5214 is a "nicotinic channel blocker that is thought to treat depression by acting on neuronal nicotinic receptors, or NNRs, according to Targacept. Targacept says NNRs are found on nerve cells throughout the nervous system and regulate nervous system activity."
The Cholinergic Hypothesis of Depression?
среда, 23 декабря 2009 г.
Zicronapine
Zicronapine shows significant positive data in clinical phase II in the treatment of patients with schizophrenia - planning for continued clinical work
Corporate Release No 392
18 December 2009
H. Lundbeck A/S (Lundbeck) today announced strongly positive headline results
from the clinical trials in the phase II development programme with zicronapine
in schizophrenia. The programme consisted of two studies which in total involved
approximately 375 patients.
In the two recently completed randomised clinical phase II trials, zicronapine
was tested in several dosages between 3-10 mg/day. The two studies were
exploratory and therefore not powered to show clear statistical differences.
However, in the studies zicronapine did show clear statistical significant
separation from placebo at 7 and 10 mg and very convincing efficacy and safety
data when compared to olanzapine justifying further development.
In the placebo-controlled trial, zicronapine showed clear dose-response and a
statistically significant improvement in PANSS score on both 7 and 10 mg. In the
olanzapine-referenced study, zicronapine showed comparable reduction in PANSS
score.
From both trials it can be concluded that zicronapine was safe and
well-tolerated. In the olanzapine-referenced study the number of withdrawals was
similar to the level of withdrawals in the olanzapine-group.
"We are pleased to see the efficacy and supportive data enabling us to continue
the development program," says Executive Vice President Anders Gersel Pedersen,
Head of Drug Development at Lundbeck. "We are also pleased that the good safety
profile seen in earlier studies now is confirmed in a much larger patient
population.?
In the coming months, Lundbeck will finalise the planning for additional
clinical work including plans for the pivotal programme.
About the study
In the placebo-controlled clinical phase II study approximately 280 patients
from 11 countries suffering from schizophrenia were enrolled. Eligible patients
have been randomised in a 2:1 ratio to blinded treatment with either zicronapine
(3, 5, 7 and 10 mg/day) or placebo for 8 weeks. The primary focus of this trial
was safety and tolerability measured by adverse events, clinical safety
laboratory tests and metabolic parameters. Secondary outcome measures included
Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression ?
Severity/Improvement (CGI-S/I) scores.
In the second clinical phase II study approximately 93 patients were enrolled
from nine countries. Eligible patients were randomised to treatment with either
flexible doses (5-7 mg/day) of zicronapine or flexible doses of olanzapine
(10-15 mg/day) for 12 weeks. The efficacy and the safety of zicronapine were
explored in comparison to olanzapine. The primary outcome measures included the
PANSS score. Secondary outcome measures included CGI-S/I and Calgary Depression
Scale for Schizophrenia (CDSS) scores.
About zicronapine (previously known as Lu 31-130)
Zicronapine has a multi-receptorial profile. In vitro and in vivo, zicronapine
has shown potent antagonistic effects at dopamine D(1), D(2) and 5-HT(2a)
receptors. Based on the profile from antipsychotic animal models, zicronapine
was expected to show clear and convincing effects in patients with schizophrenia
and likely associated with low potential for neurological side effects and a
benign safety/tolerability profile.
schizophrenia.com
Corporate Release No 392
18 December 2009
H. Lundbeck A/S (Lundbeck) today announced strongly positive headline results
from the clinical trials in the phase II development programme with zicronapine
in schizophrenia. The programme consisted of two studies which in total involved
approximately 375 patients.
In the two recently completed randomised clinical phase II trials, zicronapine
was tested in several dosages between 3-10 mg/day. The two studies were
exploratory and therefore not powered to show clear statistical differences.
However, in the studies zicronapine did show clear statistical significant
separation from placebo at 7 and 10 mg and very convincing efficacy and safety
data when compared to olanzapine justifying further development.
In the placebo-controlled trial, zicronapine showed clear dose-response and a
statistically significant improvement in PANSS score on both 7 and 10 mg. In the
olanzapine-referenced study, zicronapine showed comparable reduction in PANSS
score.
From both trials it can be concluded that zicronapine was safe and
well-tolerated. In the olanzapine-referenced study the number of withdrawals was
similar to the level of withdrawals in the olanzapine-group.
"We are pleased to see the efficacy and supportive data enabling us to continue
the development program," says Executive Vice President Anders Gersel Pedersen,
Head of Drug Development at Lundbeck. "We are also pleased that the good safety
profile seen in earlier studies now is confirmed in a much larger patient
population.?
In the coming months, Lundbeck will finalise the planning for additional
clinical work including plans for the pivotal programme.
About the study
In the placebo-controlled clinical phase II study approximately 280 patients
from 11 countries suffering from schizophrenia were enrolled. Eligible patients
have been randomised in a 2:1 ratio to blinded treatment with either zicronapine
(3, 5, 7 and 10 mg/day) or placebo for 8 weeks. The primary focus of this trial
was safety and tolerability measured by adverse events, clinical safety
laboratory tests and metabolic parameters. Secondary outcome measures included
Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression ?
Severity/Improvement (CGI-S/I) scores.
In the second clinical phase II study approximately 93 patients were enrolled
from nine countries. Eligible patients were randomised to treatment with either
flexible doses (5-7 mg/day) of zicronapine or flexible doses of olanzapine
(10-15 mg/day) for 12 weeks. The efficacy and the safety of zicronapine were
explored in comparison to olanzapine. The primary outcome measures included the
PANSS score. Secondary outcome measures included CGI-S/I and Calgary Depression
Scale for Schizophrenia (CDSS) scores.
About zicronapine (previously known as Lu 31-130)
Zicronapine has a multi-receptorial profile. In vitro and in vivo, zicronapine
has shown potent antagonistic effects at dopamine D(1), D(2) and 5-HT(2a)
receptors. Based on the profile from antipsychotic animal models, zicronapine
was expected to show clear and convincing effects in patients with schizophrenia
and likely associated with low potential for neurological side effects and a
benign safety/tolerability profile.
schizophrenia.com
вторник, 22 декабря 2009 г.
SNRIs Anti-depressants
Trazodone (Desyrel) inhibits serotonin reuptake in addition to blocking certain types of serotonin, norepinephrine, and histamine receptors. Histamine is a both a biological chemical involved in immune responses as well as a neurotransmitter. In low doses, Trazodone can be used as a sleep aid, especially for people who experience insomnia as part of their depression. Side effects of Trazodone include: allergic reactions, irregular heartbeat, prolonged and painful erection, drowsiness, fatigue, lethargy (exhaustion), psychomotor retardation (slow movements), lightheadedness, dizziness, difficulty concentrating, confusion, impaired memory, disorientation, excitement, agitation, anxiety, tension, nervousness, restlessness, insomnia, nightmares, anger, hostility and, rarely, hypomania, visual distortions, hallucinations (sensing things that aren't really there), delusions (false, fixed beliefs), and paranoia (suspicious fear).
Buproprion (Wellbutrin) is often a first choice treatment for Major Depressive Disorder. This medication is just as effective as SSRIs in treating depressive symptoms, with less risk of weight gain and sexual side effects. In addition to serotonin and norepinephrine, buproprion also inhibits dopamine reuptake. The most common side effects of buproprion are dry mouth, constipation, headaches, and insomnia. Care must be taken when using buproprion at higher doses, as it has been known to cause seizures.
Venlafaxine (Effexor) is often used for the treatment of depressive illnesses, but large numbers of studies demonstrating treatment success are lacking. In addition to inhibiting serotonin reuptake, venlafaxine inhibits norepinephrine and dopamine reuptake. Venlafaxine does not interfere with other brain chemicals, which makes it less "messy" and more powerful than other antidepressants. Some evidence suggests that venlafaxine relieves depressive symptoms more quickly than other medications with fewer side effects, and that it can be combined safely with other medications. However, more research is necessary to substantiate these claims.
Nefazodone (Serzone) inhibits serotonin reuptake by blocking a particular type of serotonin receptor. Serzone is sedating, and is useful for relieving anxiety and severe insomnia. Furthermore, sexual side effects are mild, if any. Unfortunately however, nefazodone is a strong inhibitor of liver enzymes and should be used cautiously. Many medications are metabolized in the liver, and functional liver enzymes are essential to proper liver functioning and overall health.
Mirtazapine (Remeron) blocks serotonin and norepinephrine reuptake. Mirtazapine is sedating, and has the disagreeable side effect (for most) of weight gain in comparison with other SSRIs. Although few studies clearly demonstrate Mirtazapine's usefulness in treating unipolar depression, this medication may be a good option for people who have experienced significant weight loss during their depressive episodes.
Antidepressants for Major Depression - Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRI)
Trazodone (Desyrel) inhibits serotonin reuptake in addition to blocking certain types of serotonin, norepinephrine, and histamine receptors. Histamine is a both a biological chemical involved in immune responses as well as a neurotransmitter. In low doses, Trazodone can be used as a sleep aid, especially for people who experience insomnia as part of their depression. Side effects of Trazodone include: allergic reactions, irregular heartbeat, prolonged and painful erection, drowsiness, fatigue, lethargy (exhaustion), psychomotor retardation (slow movements), lightheadedness, dizziness, difficulty concentrating, confusion, impaired memory, disorientation, excitement, agitation, anxiety, tension, nervousness, restlessness, insomnia, nightmares, anger, hostility and, rarely, hypomania, visual distortions, hallucinations (sensing things that aren't really there), delusions (false, fixed beliefs), and paranoia (suspicious fear).
Buproprion (Wellbutrin) is often a first choice treatment for Major Depressive Disorder. This medication is just as effective as SSRIs in treating depressive symptoms, with less risk of weight gain and sexual side effects. In addition to serotonin and norepinephrine, buproprion also inhibits dopamine reuptake. The most common side effects of buproprion are dry mouth, constipation, headaches, and insomnia. Care must be taken when using buproprion at higher doses, as it has been known to cause seizures.
Venlafaxine (Effexor) is often used for the treatment of depressive illnesses, but large numbers of studies demonstrating treatment success are lacking. In addition to inhibiting serotonin reuptake, venlafaxine inhibits norepinephrine and dopamine reuptake. Venlafaxine does not interfere with other brain chemicals, which makes it less "messy" and more powerful than other antidepressants. Some evidence suggests that venlafaxine relieves depressive symptoms more quickly than other medications with fewer side effects, and that it can be combined safely with other medications. However, more research is necessary to substantiate these claims.
Nefazodone (Serzone) inhibits serotonin reuptake by blocking a particular type of serotonin receptor. Serzone is sedating, and is useful for relieving anxiety and severe insomnia. Furthermore, sexual side effects are mild, if any. Unfortunately however, nefazodone is a strong inhibitor of liver enzymes and should be used cautiously. Many medications are metabolized in the liver, and functional liver enzymes are essential to proper liver functioning and overall health.
Mirtazapine (Remeron) blocks serotonin and norepinephrine reuptake. Mirtazapine is sedating, and has the disagreeable side effect (for most) of weight gain in comparison with other SSRIs. Although few studies clearly demonstrate Mirtazapine's usefulness in treating unipolar depression, this medication may be a good option for people who have experienced significant weight loss during their depressive episodes.
Antidepressants for Major Depression - Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRI)
"Why does this matter? Because the two scales used to rate depression in this study, the Hamilton Scale and the Montgomery-Asberg Scale, both count reduced appetite and sleeplessness as symptoms of depression. If you're on mirtazapine, you're unlikely to have either problem - you'll be more worried about the exact opposite, insatiable hunger and drowsiness. So mirtazapine could reduce your total score on these scales even if it didn't change your mood. I have no idea to what extent this is a factor in these results, but it could be important."
Two Drugs Are Better Than One?
четверг, 17 декабря 2009 г.
ранний ответ на терапию как предиктор эффективности лечения рисперидоном
Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether ‘switching’ early non-responders to another antipsychotic is a better strategy than ‘staying’.
This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching’ strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.
Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia
This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching’ strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.
Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia
понедельник, 14 декабря 2009 г.
сравнение высоких и низких доз кветиапина в терапии шизофрении
BACKGROUND: Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d). METHODS: In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests. RESULTS: Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters. CONCLUSIONS: Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.
Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.
Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.
коррекция акатизии вызванной нейролептиками при помощи пиридоксина
his study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design.
The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037).
Vitamin B6 Treatment in Acute Neuroleptic-Induced Akathisia: A Randomized, Double-Blind, Placebo-Controlled Study.
The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037).
Vitamin B6 Treatment in Acute Neuroleptic-Induced Akathisia: A Randomized, Double-Blind, Placebo-Controlled Study.
пятница, 11 декабря 2009 г.
среда, 9 декабря 2009 г.
вторник, 8 декабря 2009 г.
понедельник, 7 декабря 2009 г.
пятница, 4 декабря 2009 г.
депривация сна
Ms. W’s chronotherapy protocol: Hours permitted for sleep*
Day number | |||||
| 1 | 2 | 3 | 4 | 5 |
Sleep deprivation | 9 PM to2 AM |
|
|
|
|
Sleep-phase advance |
| 5 PM to midnight | 7 PM to 2 AM | 9 PM to 4 AM | 10 PM to 5 AM |
*Treatment was implemented while Ms. W was hospitalized | |||||
The bedtime solution
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