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Re: Why is klonopin acting like an AD?! » Kon

Posted by chemist on May 16, 2004, at 20:45:15

In reply to Re: Why is klonopin acting like an AD?!, posted by Kon on May 16, 2004, at 19:46:15

for what it's worth, i am confused myself....seems like there are some contradictory studies....to the best of my knowledge, the triazolo derivatives are better quantified with some AD properties, but the traditional 1,4- and 1,5-substituted benzos remain a mystery to me in re: AD activity....all the best, chemist

> There are some studies suggesting that klonopin can have AD effects, so your response is not unheard of. I've posted two klonopin AD studies below. However, there are also studies suggesting that klonopin may induce depression as a side-effect in some individuals. So it seems klonopin's response wrt depression is variable.
>
> I don't think anybody really knows why klonopin can act as an AD in some subjects and induce depression in others. Klonopin's effect wrt serotonin also seems to vary. Some studies suggest a decrease in the activity of the serotonergic systems, others studies suggest an increase. I've posted a few quotes from studies below especially wrt decrease in serotonin. It seems pretty confusing (or at least I'm damn confused).
>
>
> 1. AD effects of klonopin:
>
> Acta Psychiatr Scand. 1988 Jan;77(1):81-6.
>
> Treatment of depression with clonazepam.
>
> The antidepressive effect of an anticonvulsant clonazepam was studied with maximum daily dose of 1.5 to 6.0 mg (mean 3.4 mg) in 27 patients with major depression (n = 18) or bipolar disorder (n = 9). Two of them dropped out at an early stage of the treatment, and the antidepressive effect of clonazepam was evaluated for the remaining 25 patients. A marked to moderate improvement was obtained for 21 patients (84%), and the onset of the antidepressive effect of clonazepam appeared within 1 week in most of the cases who responded to the therapy. The total scores on the Hamilton Depression Rating Scale and the Beck Self-Rating Scale were significantly reduced after the clonazepam treatment. Side effects occurred in 14 patients, but most of them were not severe. From these results, it is thought that clonazepam might be useful as an antidepressant for patients in whom conventional antidepressant treatment are contraindicated
>
> Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Jun;22(3):97-101.
>
> Clonazepam in the treatment of protracted depression: a hundred-case report
>
> Clonazepam, which presently is recommended for the treatment of seizure disorders, has been reported to be useful as an adjunctive treatment for depression. The purpose of this paper was to examine the suitable adjunctive dose and the characteristics of clonazepam for the treatment of protracted depression. A hundred protracted depressive patients treated with clonazepam were studies by the retrospective method. A daily dose of 3.0 mg clonazepam as augmentation expressed high effectiveness (78.4%) on protracted depression. Most of the improved patients showed a rapid onset of action within two weeks. Gender, age, phase number, family history of psychosis, and clinical symptoms did not change the effectiveness of clonazepam treatment. A daily dose of at least 3.0 mg clonazepam as augmentation of ongoing antidepressant treatment should be considered for protracted depressive patients with suboptimal improvement. Unipolar depression was significantly more effective than bipolar depression on clonazepam treatment. The clear-cut difference in response to unipolar and bipolar depression suggests that the underlying abnormality in unipolar depression is not the same as that in bipolar depression. A continuance of clonazepam after improvement disturbed the recurrence of depression, and it seems that clonazepam augmentation has a preventive effect.
>
> --------------------------------------------------
> 2. Klonopin and serotonin:
>
> From Moroz (2004):
> "...in addition, unlike many other benzodiazepines, clonazepam up-regulates the serotonin-1 and serotonin –2 (5-HT1 and 5HT2) receptors. This serotonergic effect may underlie the drug’s antimyoclonic and some of its psychotropic effects."
>
> From Reiter et al. (1990):
> "Its mechanism of action in these disorders is unclear but may be related to its affinity for benzodiazepines receptors or its serotonergic effects."
>
> Lima et al (1993):
> "Clonazepam is one of the most potent benzodiazepines known to decrease the activity of the central serotonergic systems."
>
> Wagner et al. (1986):
> "These data suggest that serotonin receptor changes seen after chronic clonazepam may occur as a compensatory response to decreases in the presynaptic release of serotonin."
>
> Pratt (1979):
> "Clonazepam induces decreased serotoninergic activity in the mouse brain"
>


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