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Klonopin, depression, unipolar vs bipolar...long

Posted by blueberry on June 16, 2006, at 17:12:13

Since my doc wants me on klonopin, I had to study up on it. Included here is lots of reading for those interested. The general findings are:
Klonopin works well for unipolar depression but not bipolar depression. It can accelerate response to ssri. It alone can be a good antidepressant. There are many flaws and shortcomings to the trials, so these are just generalizations. It makes me wonder why so many people here at pbabble get depressed on klono, that is, unless maybe it is because the dose was too low or they were bipolar. One study in particular was eye opening...80% of unipolar patients responded with an 80% reduction of symptoms, wow, that's huge, but only 10% of bipolar patients responded. Enjoy...

[Clonazepam as a therapeutic adjunct to improve the management of depression]

[Article in Japanese]

Morishita S.

Depression Prevent Medical Center, Jujo Hospital, 32 Hattandacho, Kishoin, Minami-ku, Kyoto, 601-8325 Japan.

Clonazepam, which is a benzodiazepine structurally related to chlordiazepoxide hydrochloride, diazepam and nitrazepam, has been available for the treatment of seizure disorders in the USA since 1976 and in Japan since 1981. Increasingly, clonazepam has been used in the treatment of a variety of psychiatric disorders. The effect of clonazepam on depression was first reported by Jones and Chouinard in 1985. Since their report, many investigators have reported on the antidepressive properties of clonazepam. A daily dose of at least 3.0 mg clonazepam in augmentation of ongoing antidepressant treatment should be considered in depression. Regarding clonazepam augmentation therapy, if a patient does not show improvement by the end of four weeks, the treatment regimen should be altered. Age at onset of the first depressive episode and a history of family psychiatric illness should be considered the predictor of prognosis. The author discusses specific guidelines for the use of clonazepam in depression.

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

Winkler D, Willeit M, Wolf R, Stamenkovic M, Tauscher J, Pjrek E, Konstantinidis A, Schindler S, Barnas C, Kasper S.

Department of General Psychiatry, University Hospital for Psychiatry, Wahringer Gurtel 18-20, A-1090, Vienna, Austria. dietmar.winkler@akh-wien.ac.at

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.

Clonazepam augmentation of antidepressants: does it distinguish unipolar from bipolar depression?

Morishita S, Aoki S.

Department of Psychiatry, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. morisita@med.kawasaki-m.ac.jp

BACKGROUND: The authors compared the effect of clonazepam supplement treatment on unipolar depression and bipolar depression. METHODS: A total of 38 protracted depression patients with unipolar depression (n = 19) or bipolar depression (n = 19) were treated with 3.0 mg clonazepam for 4 weeks. RESULTS: In the unipolar depression group, 84.2% of the subjects fulfilled the response criteria (at least an 80% reduction in their HDRS score). However, in the bipolar depression group, only 10.5% of them fulfilled these criteria. CONCLUSIONS: The difference in responses between the two groups supposes that the underlying abnormality in unipolar depression is not the same as that in bipolar depression. This trial also supposed that clonazepam can play active role in the treatment of protracted depression in patients with unipolar depression. LIMITATIONS: This finding was made in an open study, and the effect on clonazepam alone was not established.

Clonazepam in the treatment of protracted depression: a hundred-case report]

[Article in Japanese]

Morishita S.

Department of Psychiatry, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan.

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.

Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?

Smith WT, Londborg PD, Glaudin V, Painter JR; Summit Research Network.

Summit Research Network, 1849 NW Kearney, Portland, OR 97209, USA. wsmith@summitnetwork.com

BACKGROUND: Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension. METHOD: Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months. RESULTS: No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy. LIMITATIONS: Small sample size (N=50) limited power and rendered conclusions tentative. CONCLUSIONS: Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.

Clonazepam in the treatment of prolonged depression.

Morishita S, Aoki S.

Department of Psychiatry, Kawasaki Medical School, Kurashiki, Japan.

BACKGROUND: The purpose of this paper was to examine the optimal adjunctive dose of clonazepam for the treatment of prolonged depression. METHODS: Sixty nine patients with prolonged depression were enrolled in an open trial over a 4 week period during which clonazepam was added to their medication. RESULTS: A daily dose of 3.0 mg clonazepam as augmentation was significantly more effective than doses of 1.5 mg and below. Most of the improved patients showed a rapid onset of action within 2 weeks, and side effects were not severe. CONCLUSION: A daily dose of at least 3.0 mg clonazepam as augmentation of ongoing antidepressant treatment should be considered in prolonged depressive patients with suboptimal improvement. LIMITATIONS: The effect on clonazepam alone on prolonged depression was not established, and its effect of on severe depression is unknown. High dose treatment was not carried out in this study.

Effectiveness of clonazepam in depressive disorders]

[Article in Czech]

Svestka J, Ceskova E, Kamenicka V, Buresova A.

Psychiatricka klinika LF MU a FNsP Brno-Bohunice.

Clonazepam was administered to 55 patients with depressive disorder (DSM-III-R) in average minimal and maximal doses of 2.40 and 6.54 mg/day for 21-28 days. Complete remission was achieved in 60% patients (Serejskij AB, drop of global HAMD and FKD score by more than 50%), in particular in case of concurrent anxiety. A marked antidepressive effectiveness of clonazepam was suggested also by a drop of the total HAMD and FKD score already after the first week of treatment. All items of the HAMD and FKD scale were significantly positively influenced with the exception of agitation, somatic anxiety, insight, paranoidity, obsession respectively hypochondriasis and paranoidity. No correlation was found between the effect of clonazepam and sex, the patients' age, duration of the depressive disorder, period of the index episode and severity of depression. As to undesirable effects, the authors recorded fatigue and sleepiness (40%) and hypotension (20% of the patients), in particular at the onset of treatment and after larger daily doses. In 3/10 bipolar patients a switch to hypomania was observed.

Treatment of depression with clonazepam.

Kishimoto A, Kamata K, Sugihara T, Ishiguro S, Hazama H, Mizukawa R, Kunimoto N.

Department of Neuropsychiatry, Tottori University School of Medicine, Yonago, Japan.

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.


[Clonazepam as a therapeutic adjunct to improve the management of depression]

[Article in Japanese]

Morishita S.

Depression Prevent Medical Center, Jujo Hospital, 32 Hattandacho, Kishoin, Minami-ku, Kyoto, 601-8325 Japan.

Clonazepam, which is a benzodiazepine structurally related to chlordiazepoxide hydrochloride, diazepam and nitrazepam, has been available for the treatment of seizure disorders in the USA since 1976 and in Japan since 1981. Increasingly, clonazepam has been used in the treatment of a variety of psychiatric disorders. The effect of clonazepam on depression was first reported by Jones and Chouinard in 1985. Since their report, many investigators have reported on the antidepressive properties of clonazepam. A daily dose of at least 3.0 mg clonazepam in augmentation of ongoing antidepressant treatment should be considered in depression. Regarding clonazepam augmentation therapy, if a patient does not show improvement by the end of four weeks, the treatment regimen should be altered. Age at onset of the first depressive episode and a history of family psychiatric illness should be considered the predictor of prognosis. The author discusses specific guidelines for the use of clonazepam in depression.

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

Winkler D, Willeit M, Wolf R, Stamenkovic M, Tauscher J, Pjrek E, Konstantinidis A, Schindler S, Barnas C, Kasper S.

Department of General Psychiatry, University Hospital for Psychiatry, Wahringer Gurtel 18-20, A-1090, Vienna, Austria. dietmar.winkler@akh-wien.ac.at

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.

Clonazepam augmentation of antidepressants: does it distinguish unipolar from bipolar depression?

Morishita S, Aoki S.

Department of Psychiatry, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. morisita@med.kawasaki-m.ac.jp

BACKGROUND: The authors compared the effect of clonazepam supplement treatment on unipolar depression and bipolar depression. METHODS: A total of 38 protracted depression patients with unipolar depression (n = 19) or bipolar depression (n = 19) were treated with 3.0 mg clonazepam for 4 weeks. RESULTS: In the unipolar depression group, 84.2% of the subjects fulfilled the response criteria (at least an 80% reduction in their HDRS score). However, in the bipolar depression group, only 10.5% of them fulfilled these criteria. CONCLUSIONS: The difference in responses between the two groups supposes that the underlying abnormality in unipolar depression is not the same as that in bipolar depression. This trial also supposed that clonazepam can play active role in the treatment of protracted depression in patients with unipolar depression. LIMITATIONS: This finding was made in an open study, and the effect on clonazepam alone was not established.

Clonazepam in the treatment of protracted depression: a hundred-case report]

[Article in Japanese]

Morishita S.

Department of Psychiatry, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan.

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.

Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?

Smith WT, Londborg PD, Glaudin V, Painter JR; Summit Research Network.

Summit Research Network, 1849 NW Kearney, Portland, OR 97209, USA. wsmith@summitnetwork.com

BACKGROUND: Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension. METHOD: Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months. RESULTS: No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy. LIMITATIONS: Small sample size (N=50) limited power and rendered conclusions tentative. CONCLUSIONS: Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.

Clonazepam in the treatment of prolonged depression.

Morishita S, Aoki S.

Department of Psychiatry, Kawasaki Medical School, Kurashiki, Japan.

BACKGROUND: The purpose of this paper was to examine the optimal adjunctive dose of clonazepam for the treatment of prolonged depression. METHODS: Sixty nine patients with prolonged depression were enrolled in an open trial over a 4 week period during which clonazepam was added to their medication. RESULTS: A daily dose of 3.0 mg clonazepam as augmentation was significantly more effective than doses of 1.5 mg and below. Most of the improved patients showed a rapid onset of action within 2 weeks, and side effects were not severe. CONCLUSION: A daily dose of at least 3.0 mg clonazepam as augmentation of ongoing antidepressant treatment should be considered in prolonged depressive patients with suboptimal improvement. LIMITATIONS: The effect on clonazepam alone on prolonged depression was not established, and its effect of on severe depression is unknown. High dose treatment was not carried out in this study.

Effectiveness of clonazepam in depressive disorders]

[Article in Czech]

Svestka J, Ceskova E, Kamenicka V, Buresova A.

Psychiatricka klinika LF MU a FNsP Brno-Bohunice.

Clonazepam was administered to 55 patients with depressive disorder (DSM-III-R) in average minimal and maximal doses of 2.40 and 6.54 mg/day for 21-28 days. Complete remission was achieved in 60% patients (Serejskij AB, drop of global HAMD and FKD score by more than 50%), in particular in case of concurrent anxiety. A marked antidepressive effectiveness of clonazepam was suggested also by a drop of the total HAMD and FKD score already after the first week of treatment. All items of the HAMD and FKD scale were significantly positively influenced with the exception of agitation, somatic anxiety, insight, paranoidity, obsession respectively hypochondriasis and paranoidity. No correlation was found between the effect of clonazepam and sex, the patients' age, duration of the depressive disorder, period of the index episode and severity of depression. As to undesirable effects, the authors recorded fatigue and sleepiness (40%) and hypotension (20% of the patients), in particular at the onset of treatment and after larger daily doses. In 3/10 bipolar patients a switch to hypomania was observed.

Treatment of depression with clonazepam.

Kishimoto A, Kamata K, Sugihara T, Ishiguro S, Hazama H, Mizukawa R, Kunimoto N.

Department of Neuropsychiatry, Tottori University School of Medicine, Yonago, Japan.

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.



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