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Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis
A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary...
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| Published in: | Molecular psychiatry 2021-01, Vol.26 (1), p.118-133 |
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| creator | Kato, Masaki Hori, Hikaru Inoue, Takeshi Iga, Junichi Iwata, Masaaki Inagaki, Takahiko Shinohara, Kiyomi Imai, Hissei Murata, Atsunobu Mishima, Kazuo Tajika, Aran |
| description | A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies (
n
= 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33–0.43,
p
|
| doi_str_mv | 10.1038/s41380-020-0843-0 |
| format | article |
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n
= 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33–0.43,
p
< 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17–0.50,
p
< 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28–0.38,
p
< 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36–0.54,
p
< 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23–0.48,
p
< 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36–0.48,
p
< 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29–0.55,
p
< 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35–0.48,
p
< 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29–0.41,
p
< 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40–0.55,
p
< 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18–0.64,
p
= 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.]]></description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-020-0843-0</identifier><identifier>PMID: 32704061</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/53/2422 ; 692/699/476/1414 ; Antidepressants ; Antidepressive Agents - administration & dosage ; Antidepressive Agents - therapeutic use ; Antidepressive Agents, Tricyclic - administration & dosage ; Antidepressive Agents, Tricyclic - therapeutic use ; Behavioral Sciences ; Biological Psychology ; Clinical significance ; Controlled Clinical Trials as Topic ; Depression - drug therapy ; Depressive Disorder, Major - drug therapy ; Drug therapy ; Humans ; Major depressive disorder ; Medicine ; Medicine & Public Health ; Mental depression ; Meta-analysis ; Neurosciences ; Patient outcomes ; Pharmacotherapy ; Placebos ; Psychiatry ; Regression (Disease) ; Remission ; Remission (Medicine) ; Remission Induction ; Review ; Review Article ; Selective Serotonin Reuptake Inhibitors - administration & dosage ; Selective Serotonin Reuptake Inhibitors - therapeutic use ; Systematic review</subject><ispartof>Molecular psychiatry, 2021-01, Vol.26 (1), p.118-133</ispartof><rights>The Author(s) 2020</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-ebd8a0922f259b5678c5e40767e26e6b76de03650315cba767ed0c3f15797c513</citedby><cites>FETCH-LOGICAL-c537t-ebd8a0922f259b5678c5e40767e26e6b76de03650315cba767ed0c3f15797c513</cites><orcidid>0000-0002-6143-0181 ; 0000-0003-4409-3096 ; 0000-0001-6727-7272</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32704061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kato, Masaki</creatorcontrib><creatorcontrib>Hori, Hikaru</creatorcontrib><creatorcontrib>Inoue, Takeshi</creatorcontrib><creatorcontrib>Iga, Junichi</creatorcontrib><creatorcontrib>Iwata, Masaaki</creatorcontrib><creatorcontrib>Inagaki, Takahiko</creatorcontrib><creatorcontrib>Shinohara, Kiyomi</creatorcontrib><creatorcontrib>Imai, Hissei</creatorcontrib><creatorcontrib>Murata, Atsunobu</creatorcontrib><creatorcontrib>Mishima, Kazuo</creatorcontrib><creatorcontrib>Tajika, Aran</creatorcontrib><title>Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description><![CDATA[A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies (
n
= 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33–0.43,
p
< 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17–0.50,
p
< 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28–0.38,
p
< 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36–0.54,
p
< 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23–0.48,
p
< 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36–0.48,
p
< 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29–0.55,
p
< 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35–0.48,
p
< 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29–0.41,
p
< 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40–0.55,
p
< 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18–0.64,
p
= 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.]]></description><subject>692/53/2422</subject><subject>692/699/476/1414</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - administration & dosage</subject><subject>Antidepressive Agents - therapeutic use</subject><subject>Antidepressive Agents, Tricyclic - administration & dosage</subject><subject>Antidepressive Agents, Tricyclic - therapeutic use</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Clinical significance</subject><subject>Controlled Clinical Trials as Topic</subject><subject>Depression - drug therapy</subject><subject>Depressive Disorder, Major - drug therapy</subject><subject>Drug therapy</subject><subject>Humans</subject><subject>Major depressive disorder</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental depression</subject><subject>Meta-analysis</subject><subject>Neurosciences</subject><subject>Patient outcomes</subject><subject>Pharmacotherapy</subject><subject>Placebos</subject><subject>Psychiatry</subject><subject>Regression (Disease)</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Remission Induction</subject><subject>Review</subject><subject>Review Article</subject><subject>Selective Serotonin Reuptake Inhibitors - 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Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies (
n
= 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33–0.43,
p
< 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17–0.50,
p
< 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28–0.38,
p
< 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36–0.54,
p
< 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23–0.48,
p
< 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36–0.48,
p
< 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29–0.55,
p
< 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35–0.48,
p
< 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29–0.41,
p
< 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40–0.55,
p
< 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18–0.64,
p
= 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.]]></abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32704061</pmid><doi>10.1038/s41380-020-0843-0</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-6143-0181</orcidid><orcidid>https://orcid.org/0000-0003-4409-3096</orcidid><orcidid>https://orcid.org/0000-0001-6727-7272</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1359-4184 |
| ispartof | Molecular psychiatry, 2021-01, Vol.26 (1), p.118-133 |
| issn | 1359-4184 1476-5578 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7815511 |
| source | Springer Nature; Alma/SFX Local Collection |
| subjects | 692/53/2422 692/699/476/1414 Antidepressants Antidepressive Agents - administration & dosage Antidepressive Agents - therapeutic use Antidepressive Agents, Tricyclic - administration & dosage Antidepressive Agents, Tricyclic - therapeutic use Behavioral Sciences Biological Psychology Clinical significance Controlled Clinical Trials as Topic Depression - drug therapy Depressive Disorder, Major - drug therapy Drug therapy Humans Major depressive disorder Medicine Medicine & Public Health Mental depression Meta-analysis Neurosciences Patient outcomes Pharmacotherapy Placebos Psychiatry Regression (Disease) Remission Remission (Medicine) Remission Induction Review Review Article Selective Serotonin Reuptake Inhibitors - administration & dosage Selective Serotonin Reuptake Inhibitors - therapeutic use Systematic review |
| title | Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis |
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