Short-Term Augmentation of Fluoxetine With Clonazepam in the Treatment of Depression: A Double-Blind Study

Smith, Ward T.; Londborg, Peter D.; Glaudin, Vincent; Painter, John R.

doi:10.1176/ajp.155.10.1339

Cited by 83 publications

(43 citation statements)

References 39 publications

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“…Conventional antidepressants typically feature a 2-to 6-week delay in response onset, and benzodiazepines have been used for augmentation to reduce the agitation, anxiety, and insomnia associated with depression. Smith et al conducted a double-blind study to determine which was superior for major depression, a combination of clonazepam and fluoxetine or monotherapy with fluoxetine (Smith et al, 1998). Combination therapy of clonazepam and fluoxetine improved major depression significantly more during the first 3 weeks of treatment.…”

Section: Indicationsmentioning

confidence: 99%

“…Svestka et al (1995) reported that clonazepam treatment for 3-4 weeks achieved complete remission in 60% of 55 patients with depressive disorder. Smith et al (1998) reported that in an 8-week, double blind study in 80 patients with major depression, the combination of clonazepam and fluoxetine was superior to fluoxetine monotherapy in relieving symptoms of moderate to marked depression, especially during the first 3 weeks. In addition, in 10 days, the combination of clonazepam and fluoxetine achieved the same improvement as obtained with fluoxetine alone by day 56.…”

Section: Optimal Dose and Appropriate Duration Of Treatmentmentioning

confidence: 99%

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Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review

Morishita

2009

Human Psychopharmacology

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Clonazepam, first used for seizure disorders, is now increasingly used to treat affective disorders. We summarize the use of clonazepam to improve the management of depression. Clonazepam is useful for treatment-resistant and/or protracted depression, as well as for acceleration of response to conventional antidepressants. Clonazepam is at this time recommended for use in combination with SSRIs (fluoxetine, fluvoxamine, sertraline) as an antidepressant, and should be used at a dosage of 2.5-6.0 mg/day. If clonazepam is effective, a response should be observed within 2-4 weeks. It is significantly more effective for unipolar than for bipolar depression. Low-dose, long-term treatment with clonazepam exhibits a prophylactic effect against recurrence of depression. Although the mechanism of action of clonazepam has not yet been established, some investigators have been suggested that it involves enhancement of anti-anxiety effects, anticonvulsant effects on subclinical epilepsy, increase in 5-HT/monoamine synthesis or decrease in 5-HT receptor sensitivity mediated through the GABA system, and regulate in GABA activity.

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Section: Indicationsmentioning

confidence: 99%

Section: Optimal Dose and Appropriate Duration Of Treatmentmentioning

confidence: 99%

Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review

Morishita

2009

Human Psychopharmacology

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“…Further, it is reported that SSRIs affect sleep patterns and reduce rapid eye movement (REM) sleep during early phases of treatment, as are reports of increased anxiety and nervousness. [47][48][49][50][51] A number of transcripts show up-and downregulation depending on brain region and/or treatment All three antidepressant treatments induced up-and downregulation of transcripts level. While upregulation was more frequent overall, downregulation was recorded with similar frequency in all brain regions following all three treatments.…”

Section: Number Of Transcripts Affected By Single and Multiple Treatmmentioning

confidence: 99%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.

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“…Adding of a benzodiazepine to an SSRI can provide more rapid symptom relief in depression and more rapid stabilization of panic or social phobia symptoms than the SSRI alone. [20][21][22][23] Benzodiazepines are not recommended as monotherapy in depression, as they primarily improve the symptoms of insomnia and restlessness, rather than the core depressive symptoms of sadness, anhedonia, and low energy. 24 In our study the mean age was 36 years, majority of participants were between 26-35 years, indicating a peak occurrence in 2 nd and 3 rd decades of life.…”

Section: Discussionmentioning

confidence: 99%

Addition of benzodiazepines to selective serotonin reuptake inhibitors to optimize treatment of depression: a hospital based study

2018

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Background: Selective serotonin reuptake inhibitors ameliorate depression and anxiety slowly and in fact increase anxiety or insomnia initially. Addition of clonazepam to escitalopram improves response: thereby improving symptoms associated with depression, reducing side-effects and alleviating core depressive symptoms. The aim of study was to assess the benefits of adding benzodiazepines in management of depression.Methods: It was an open label prospective study of 8 weeks of escitalopram group versus escitalopram with benzodiazepine group in moderate to severe depression. 51 subjects who gave written informed consent and were fulfilling the inclusion and exclusion criteria were included in the study and grouped into escitalopram alone or escitalopram with benzodiazepines.Results: In the present study nearly 60% of the patients were prescribed clonazepam. Though combined group with benzodiazepines had faster onset of action in controlling depressive symptoms than escitalopram group alone at 4 weeks of treatment, there was no significant difference in the pattern of reduction of MADRS score in both the groups at 8 weeks of follow up.Conclusions: Augmenting benzodiazepines to antidepressants are more effective in management of depression associated anxiety and sleep disturbances initially till SSRIs start action.

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Short-Term Augmentation of Fluoxetine With Clonazepam in the Treatment of Depression: A Double-Blind Study

Abstract: Clonazepam augmentation of fluoxetine was superior to fluoxetine alone in the first 3 weeks of treatment. This strategy may reduce suffering during early SSRI treatment, may partially suppress SSRI side effects, may increase compliance, and could possibly reduce the risk of suicide.

Cited by 83 publications

References 39 publications

Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review

Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Addition of benzodiazepines to selective serotonin reuptake inhibitors to optimize treatment of depression: a hospital based study

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