Posted by ed_uk2010 on February 10, 2012, at 12:58:56
In reply to Re: Cariprazine - Great news, hopefully. » ed_uk2010, posted by SLS on February 10, 2012, at 7:39:24
>Perhaps this would increase treatment compliance with cariprazine when treating psychotic disorders and make the drug more tolerable for people using it for depression.
In the manufacturer's trials, akathisia was one of the most frequently reported side effects. This does not surprise me. In depression, the risk of withdrawal due to adverse effects is probably dose-dependent, but seems fairly low overall.
The four main trials on the Gedeon Richter website. My summary...
The Phase III trial in acute mania.
Dose: 3-12mg per day.
Outcome: The drug was more effective than placebo.
Withdrawal due to adverse effects: 10% on cariprazine, 7% on placebo.The Phase IIb trial in schizophrenia.
Dose: Fixed dose group on 1.5mg, 3mg and 4.5mg.
Outcome: All doses were statistically better than placebo.
Dose-dependent efficacy: 4.5mg produced a numerically greater reduction in the PANSS score than 3mg, and 3mg produced a numerically greater reduction than 1.5mg. It was not reported whether these differences were statistically significant.
Withdrawal due to adverse effects: Difficult to interpret. More patients in the placebo group dropped out due to adverse effects than in any of the cariprazine groups or the risperidone group. Presumably, the adverse effects reported in the placebo group were actually uncontrolled symptoms of psychosis, or withdrawal symptoms from the antipsychotic that patient's had been on prior to the trial.Phase II study in bipolar depression.
Dose: Two groups, 0.25mg-0.75mg or 1.5-3mg per day.
Outcome: The differences from placebo were not statistically significant.
Dose-dependent efficacy: The low dose did not appear to be effective. There was some evidence that the 1.5mg-3mg group fared better than placebo, even though the results did not achieve statistical significance. Might 4.5mg have been effective? The website says that they are considering performing a new Phase II trial with different doses.
Withdrawal due to adverse effects: 9% on 1.5-3mg, 3% on placebo. The 0.25mg-0.75mg isn't mentioned, but appears subtherapeutic.Phase II study. Cariprazine as an adjunct to an antidepressant in resistant Major Depressive Disorder.
Dose: 0.1-0.3mg or 1-2mg.
Outcome: The differences from placebo were not statistically different.
Dose-dependent efficacy: The very low dose (0.1mg to 0.3mg) did not appear to be effective. The higher dose was numerically better than placebo.
Withdrawal due to adverse effects: 3% on the higher dose and on placebo, 1% in the very low dose group.It seems that we are not going to learn much more about the efficacy of cariprazine in depression until higher doses are tested in clinical trials. 0.1mg-0.75mg did not show efficacy in MDD or bipolar depression. 1-3mg showed slight but non-significant efficacy. Given that 1.5-4.5 showed some efficacy in schizophrenia, this dose range appears to be active. Perhaps somewhere around 4.5mg would be optimal in depression? Up to 12mg was used in mania but might be excessive for depression.
poster:ed_uk2010
thread:1009756
URL: http://www.dr-bob.org/babble/20120202/msgs/1009917.html