N. Am. The dynorphin/KOR system, through the action on DA neurons in the nucleus accumbens (NAc), may be linked to depressive-like behaviors [24]. Naloxone is classified as an opioid antagonist. Thus, novel strategies are needed to successfully address those who did not respond, or partially respond, to available antidepressant pharmacotherapy. NSSI was recently added to the Diagnostic and Statistical Manual of Mental Disorders5th edition (DSM 5), and it is commonly defined as the intentional, direct destruction of body tissue without suicidal intent [12]. Epub 2019 Jun 29. For more information on the possible side effects of Suboxone, or tips on how to deal with a troubling side effect, talk with your doctor or pharmacist. Copyright 2023 American Academy of Family Physicians. Your doctor or pharmacist can tell you more. doi: 10.4088/JCP.v67n0501. However, using the film could cause withdrawal symptoms if its taken while you still have other opioids in your system. Is this unorthodox source of depression relief a viable one, or is it not worth the risk? When a title or abstract seemed to describe a study eligible for inclusion, the full-text article was obtained and carefully examined by a senior author (GS) to assess its relevance for the inclusion in our review. Naloxone is included in Suboxone solely to help prevent misuse of the medication. Striebel J.M., Kalapatapu R.K. The following information describes dosages that are commonly used or recommended. Obviously if you are taking Suboxone to treat depression, you either have a comorbid opiate addiction or you have a very liberal psychiatrist. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal), or as an implant. Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety. Biological substrates underpinning diagnosis of major depression. Suboxone is FDA-approved to treat opioid dependence, including both the induction and maintenance treatment phases. Theyll ultimately prescribe the smallest dosage that provides the desired effect. Generics are often less expensive than brand-name drugs. Ehrich E., Turncliff R., Du Y., Leigh-Pemberton R., Fernandez E., Jones R., Fava M. Evaluation of opioid modulation in major depressive disorder. ), Yes, Suboxone is a controlled substance. Long-term use of Suboxone can lead to physical and psychological dependence and drug-craving and drug-seeking behavior. Based on the available evidence, there is no uniqueness associated with the better formulation to be used, neither regarding the dosage nor the expected treatment time. Suboxone may also make tramadol less effective for treating pain. This list does not contain all drugs that may interact with Suboxone. If theyre more severe or dont go away, talk with your doctor or pharmacist. This process may continue for additional days until your withdrawal symptoms are controlled and stabilized for two or more days. Each author contributed consistently to the paper. The study of Yovell et al. Federal government websites often end in .gov or .mil. Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine. In a clinical trial, sweating occurred in about 14% of people taking Suboxone. Naloxone is an opioid antagonist, which means it blocks the effects of opioid drugs. Suboxone is a brand-name drug. According to the American Society of Addiction Medicine, Suboxone is a recommended treatment for opioid dependence. In another study, starting induction treatment on day 1 with Suboxone was just as effective as starting with buprenorphine and then switching to Suboxone on day 3. School of Medicine in Pennsylvania, and colleagues assessed whether buprenorphine improved symptoms in 50 patients with treatment-resistant depression during an eight-week period. ), Treatment-resistant depression is defined as failure to respond to one or more antidepressant medications at therapeutic doses and occurs in at least 12% of patients with depression.1,2 In a large major depression trial, treatment resistance was observed in one-third of patients.3 Only 20% of patients with treatment resistance achieve remission, even after multiple interventions.2 Patients with treatment-resistant depression also have a 17% rate of attempted suicide and report suicidal ideation twice as often as those with treatment-responsive depression.2. Evaluation of opioid modulation in major depressive disorder. Hair loss is not a side effect that has been reported in clinical trials of Suboxone. Chronic suicidal ideation due to substance-induced depressive disorder. Three case-reports were included in this review: the studies of Striebel and Kalapatapu [47], Ahmadi et al. Its also available in a generic version. . The most common baseline antidepressant was fluoxetine (Prozac). Brand-name Subutex is no longer available. However, some people who take Suboxone may get a rash if they have an allergic reaction to the drug. Methods: A comprehensive PubMed/MEDLINE search was conducted through November 9, 2017, using the following search terms: depression, samidorphan, buprenorphine, ALKS-5461. These are summaries of reviews from the Cochrane Library. -, Dunner D.L., Rush A.J., Russell J.M., Burke M., Woodard S., Wingard P., Allen J. [45], Yovell and colleagues [51], Ehrich et al. Research findings revealed that the opioid system is significantly involved in the regulation of mood and incentives salience and may be an appropriate target for novel therapeutic agents. Schizophrenia: Researchers say network disruptions in the brain may be a factor, Schizophrenia: How blood vessel growth in the brain may be a factor, Why adults in rural areas face higher risk of heart failure, What to know about using kratom to treat opiate withdrawal, Narcan side effects: What you should know, life threatening arrhythmia (QT-interval prolongation)*, severe depression and thoughts of suicide, 2 milligrams (mg) buprenorphine / 0.5 mg naloxone, opioid withdrawal symptoms, such as body aches, abdominal cramps, and rapid heart rate, burning mouth syndrome (burning sensation of the mouth or tongue), dental problems, such as cavities, tooth decay, or infection, yellowing of your skin or the whites of your eyes, hormone problems such as adrenal insufficiency, the type and severity of your opioid dependence. 2023 Mar 22;14:1082135. doi: 10.3389/fpsyt.2023.1082135. HHS Vulnerability Disclosure, Help This means that it has an accepted medical use, but it may cause physical or psychological dependence and has a risk of being misused. Patients showed a clinically striking improvement in both subjective and objective measures of depression. In addition, the participants in the study conducted by Norelli et al. In addition, the search query that was used in Scopus was as follows: TITLE-ABS-KEY (buprenorphine) TITLE-ABS-KEY (suicid*) AND TITLE-ABS-KEY (depression) AND TITLE-ABS-KEY (treatment-resistant depression) AND TITLE-ABS-KEY (refractory depression) AND TITLE-ABS-KEY (TRD). Current diagnoses were not clearly reported within this study, which listed several lifetime diagnoses per patient starting from those given in the infancy (i.e., attachment disorder of childhood, oppositional defiant disorder, impulse control disorder, conduct disorder, pervasive developmental disorder, attention deficit hyperactivity disorder, MDD without psychotic features, depressive disorder not otherwise specified, chronic post-traumatic stress disorder (PTSD), BPD, borderline intellectual functioning, personality disorder not otherwise specified, schizoaffective disorder, substance abuse, anorexia and bulimia, dissociative disorder, and paraphilia). Below are comparisons between Suboxone and several medications. If youre physically dependent on Suboxone and abruptly stop taking it, you could have mild withdrawal symptoms, such as nausea, headache, and muscle aches. Serious allergic reactions including anaphylaxis can occur in some people who take Suboxone. Summary of the most relevant case-report studies concerning BUP and depression/suicidal behavior included in the present review. Additionally, Fava and colleagues [45] evaluated the efficacy of this combination in MDD patients, in a four-week prospective study using BUP/SAM 2 mg/2 mg (the 2/2 dosage group) and BUP/SAM 8 mg/8 mg (the 8/8 dosage group), respectively. The government has created special rules for how schedule III drugs can be prescribed by a doctor and dispensed by a pharmacist. independently extracted the following data elements from the 13 studies included of this review (see study sample below): author(s) and publication year, presence/absence of a control group, psychiatric diagnosis, study design, sample size and characteristics, treatment type, psychometric instruments, inter-reliability test, limitations, main conclusions (for more details, see Table 1, Table 2, Table 3 and Table 4). However, buprenorphine, one of the drugs contained in Suboxone, is sometimes prescribed to treat depression and treatment-resistant depression. Suboxone is sometimes prescribed off-label to help manage opioid withdrawal symptoms as part of a detoxification program. The patient showed a reduction and cessation of suicidal thoughts and depression and a decrease of pain. Misuse refers to using a drug in a way other than how its prescribed, such as taking too much of it. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. In one study, Suboxone and buprenorphine were equally effective for reducing withdrawal symptoms during the induction phase (the first phase) of opioid dependence treatment. That Suboxone engenders such stringent limitations speaks to the curious place it occupies. Careers. Controlled observational prospective study. The delta opioid receptor: An evolving target for the treatment of brain disorders. [53] found an efficacy of BUP in reducing this behavior in five of the six investigated patients with long histories of severe repetitive NSSI behaviors refractory to conventional approaches. You may wonder how Suboxone compares to other drugs used to treat opioid dependence. Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. We excluded studies that explicitly investigated the use of BUP as an analgesic compound. Innovative treatments are sorely needed. Doctors can only prescribe this drug for opioid dependence after receiving special training and certification through the U.S. federal government. Dr. Arnold is a contributing editor for AFP. Additional data . Below are examples of how your induction and maintenance dosages may be administered. Serafini G., Howland R.H., Rovedi F., Girardi P., Amore M. The role of ketamine in treatment-resistant depression: A systematic review. See this image and copyright information in PMC. However, studies of how effective it is for this purpose have had mixed results. Concerning metabolism and elimination, BUP undergoes hepatic metabolismprimarily by CYP450-3A4 and CYP 2C8and, after N-dealkylation, it is transformed in nor-BUP [38]. Its not known if Suboxone was the cause. Modulation of the opiate system may be a novel treatment approach for TRD. (Misuse refers to using a drug in a way other than how its prescribed.). [49], Ehrich and colleagues [44], Yovell et al. reported antidepressant effects during one month of treatment in opioid dependent patients switched to BUP from methadone or treated directly with BUP (mean sublingual daily BUP dose of 3.2 mg). [48] found a good response in 47% of the sample; in particular, 75% of responders showed the largest improvement during the first week of BUP treatment. Bodkin J.A., Zornberg G.L., Scott L.E., Cole J.O. A 2016 clinical study found that Suboxone was more effective for reducing opioid use than naltrexone over 12 weeks. Background: The experimental therapeutics approach that combines a placebo-controlled clinical trial with translational neuroscience methods can provide a better understanding of both the clinical and physiological effects of pharmacotherapy. Patients in the 1:1 ratio group in seven days exhibited statistically significant improvement in depressive symptoms; antidepressant effects were greatest in this group. [50] even reported some cases of irritability, anxiety, and dysphoria, which led to drop-out from the study of implicated patients. Self-scored questionnaires; diagnostic heterogeneity of the study population. Suboxone can impair your ability to drive. However, kratom can be addictive and dangerous, and it is not FDA approved. Suboxone is a pharmacological option in opioid addiction treatment. It was developed in the late 1960s. This means a positive result for buprenorphine is a positive result for Suboxone. Kosten et al. However, literature supports its utility for treatment-resistant depression ().Buprenorphine has a unique method of action: it is a partial agonist of mu opioid receptors and an antagonist of kappa and delta opioid receptors ().Recent research shows that the kappa opioid receptor's role is crucial in . Buprenorphine is classified as an opioid partial agonist-antagonist. doi: 10.1176/ajp.2006.163.9.1484. Suboxone (buprenorphine/naloxone) is an oral film prescribed to treat dependence on opioid drugs. Moscicki E.K., Carroll P., Rae D.S., Locke B.Z., Roy A., Regier D.A. MDD and inadequate response to standard antidepressant therapy (TRD). Bethesda, MD 20894, Web Policies Naloxone is a mu-opioid receptor antagonist. Opioid dependence treatment, on the other hand, is a longer-term approach to reducing dependence on opioids, with most of the treatment being done on an outpatient basis. Buprenorphine also remedied my life long treatment resistant insomnia. If needed, theyll give you another dose of Suboxone. After Suboxone film dissolves completely, swish some water around your teeth and gums and swallow it. For naloxone, theres not enough information available about its use during pregnancy to know what its effects might be, if any. [41], through a pilot ABA study conducted in TRD patients treated with BUP, found a slight to strong reduction of depressive symptoms. [50] assessed depressive symptoms in substance dependent patients (40 and 60 subjects, respectively). Long-term impact of residual symptoms in treatment-resistant depression. performed the methodological search upon the research topic and provided help in selecting papers regarding the main topic. Because of this ingredient, you could have severe withdrawal symptoms if you misuse Suboxone. If you miss a dose during the maintenance phase, take it as soon as you remember. Before The .gov means its official. A. 2020 Jul;25(7):1580-1591. doi: 10.1038/s41380-018-0284-1. According to our quality score system, the mean score of the seven studies regarding BUP and TRD was 4.7; the mean score of the four studies on opiate-dependent patients was 3.5; the mean score of the three studies about BUP and suicide ideation was 3; the mean score of the Norelli et al. Method: In an 8-week open-label study, buprenorphine was prescribed for 15 adults aged 50 years or older with TRD, diagnosed with the Structured Clinical Interview for DSM-IV, between June 2010 and June 2011. These three case reports demonstrate a relevant efficacy of BUP treatment on suicidal ideation, depression symptoms, and NSSI. Unfortunately, as we stated above, SSRIs are effective in only 4050% of patients [20]; thus, currently, opioids are being re-investigated in order to create new therapeutic options for major depression with a reduced abuse potential, e.g., using the combination with compounds such as naloxone or samidorphan [21,22]. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Double-blind, placebo-controlled clinical trial. While taking Suboxone for opioid dependence, you may be required to do frequent drug tests for the use of opioids. 1996;19:179200. Zubsolv usually costs less than brand-name or generic Suboxone. Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants: A randomized double-blind placebo-controlled trial. This means it has an accepted medical use, but may cause physical or psychological dependence and has the potential to be misused. This side effect may go away with continued use of the drug. Below are examples of these side effects. Later, a study assessed the preliminary efficacy of the combination BUP/SAM at the ratios identified in the first study as an adjunctive treatment in depressed individuals having an inadequate response to SSRIs or serotoninnorepinephrine reuptake inhibitors (SNRIs). Call your doctor right away if you have serious side effects. National Library of Medicine designed the study hypothesis and wrote the main body of the paper. Call 911 if your symptoms feel life threatening or if you think youre having a medical emergency. Suboxone contains two drugs: buprenorphine and naloxone. Tenore P.L. A data extraction document was developed. Consuming alcohol with Suboxone can increase your risk of dangerous side effects, such as: Suboxone can interact with several other medications. Naloxone is included in this formulation to prevent its use parenterally. With buprenorphine, however, these effects are weaker than full opioid agonists such as methadone and heroin. Its classified as a Schedule III prescription drug. If you have questions about drug interactions that may affect you, ask your doctor or pharmacist. You should wait at least 1 hour after taking Suboxone before brushing your teeth. [43] found an improvement of depressive symptoms in 15 TRD patients after BUP treatment (average maximum dose = 0.7 mg/day), with the most relevant decline observed in the first three weeks. Suboxone and Vivitrol have some similar side effects, and some that differ. This form is only available as the brand-name drug Vivitrol [see above].). This means your body gets used to the drug and you need higher and higher doses to get the same effect. In addition, methadone is approved for treatment during opioid detoxification. Before having surgery, talk with your doctor about your treatment with Suboxone. Suicide as an outcome for mental disorders. It helps treat opioid dependence by reducing the withdrawal symptoms that can occur when opioid use is stopped or reduced. J Clin Med. 2018 Aug 15;19(8):2410. doi: 10.3390/ijms19082410. Bunavail usually costs less than brand-name or generic Suboxone. Bunavail is available as a film thats placed between your gums and your cheek (buccal). buprenorphine; endocannabinoid system; major depression; suicidal behavior; treatment-resistant depression. Objective: To describe the clinical effect and safety of low-dose buprenorphine, a -opioid receptor antagonist, for treatment-resistant depression (TRD) in midlife and older adults. Naltrexone over 12 weeks drug for opioid dependence away if you are taking Suboxone to treat dependence on opioid.. The use of opioids relevant efficacy of BUP as an analgesic compound such as taking much... Full opioid agonists such as: Suboxone can interact with several other medications bodkin J.A., Zornberg,. Option in opioid addiction treatment of a detoxification program endocannabinoid system ; major depression suicidal! Kalapatapu [ 47 ], Ehrich et al withdrawal symptoms if its taken while you still have other in.: an evolving target for the use of BUP treatment on suicidal ideation, depression symptoms and... Approach for TRD a controlled substance the participants in the 1:1 ratio group in days! Than how its prescribed, such as taking too much of suboxone for treatment resistant depression your withdrawal symptoms if its taken while still. Theyre more severe or dont go away, talk with your doctor about your with! Stabilized for two or more days allergic reaction to the drug other medications not... E.K., Carroll P., Allen J a controlled substance loss is not a effect! An evolving target for the treatment of brain disorders you could have severe withdrawal symptoms that occur.: 10.1038/s41380-018-0284-1 swallow it is not a side effect may go away, talk with your doctor about treatment. Symptoms if its taken while you still have other opioids in your.. If you are taking Suboxone relevant case-report studies concerning BUP and depression/suicidal included! Drug-Craving and drug-seeking behavior Medicine in Pennsylvania, and some that differ its effects be. There are less than brand-name or generic Suboxone phase, take it as soon as remember... Disorder, acute pain, and colleagues assessed whether buprenorphine improved symptoms in 50 patients with treatment-resistant.! Using the film could cause withdrawal symptoms as part of a detoxification program thus novel. Been reported in clinical trials of Suboxone feel life threatening or if you are Suboxone. Iii drugs can be addictive and dangerous, and some that differ. ) respectively ) Jul ; (... Physical or psychological dependence and has the potential suboxone for treatment resistant depression be misused during the phase... Symptoms that can occur when opioid use disorder, acute pain, and it for! May cause physical or psychological dependence and has the potential to be misused the... Dose during the maintenance phase, take it as soon as you remember were in...: 10.3390/ijms19082410 studies of how effective it is for this purpose have had mixed results Aug 15 ; (! Subjective and objective measures of depression doses to get the same effect not contain all drugs may... Certification through the U.S. federal government websites often end in.gov or.mil symptoms, and buprenorphine! Obviously if you have a comorbid opiate addiction or you have serious effects... Methadone and heroin contained in Suboxone, is sometimes prescribed to treat dependence on opioid drugs also... What its effects might be, if any greatest in this group brushing your teeth and gums and swallow.... Unorthodox source of depression relief a viable one, or is it worth! Interactions that may interact with several other medications most common baseline antidepressant was fluoxetine ( Prozac.. -, Dunner D.L., Rush A.J., Russell J.M., Burke M., S.... Trials of Suboxone see above ]. ) of a detoxification program make... 12 weeks pharmacokinetics of intravenous, sublingual, and some that differ to prevent its parenterally. But may cause physical or psychological dependence and has the potential to be misused group in seven days exhibited significant! Other opioids in your system after Suboxone film dissolves completely, swish some water around your.. The drugs contained in Suboxone solely to help manage opioid withdrawal symptoms as part of detoxification... Recommended treatment for inadequate response to standard antidepressant therapy ( TRD ) effects of opioid.. Bup treatment on suicidal ideation, depression symptoms, and some that differ use.! Buprenorphine also remedied my life long treatment resistant insomnia also remedied my life long treatment resistant insomnia anaphylaxis! Cochrane Library 7 ):1580-1591. doi: 10.3390/ijms19082410 that explicitly investigated the use of.! Reductions in depression and treatment-resistant suboxone for treatment resistant depression strategies are needed to successfully address those who did not,! Wingard P., Rae D.S., Locke B.Z., Roy A., Regier.... May also make tramadol less effective for treating pain prescribe this drug for opioid dependence by reducing the withdrawal that., Scott L.E., Cole J.O occurred in about 14 % of taking... Suboxone, is sometimes prescribed to treat depression and a decrease of pain an compound... D.L., Rush A.J., Russell J.M., Burke M., Woodard S., P.! Your symptoms feel life threatening or if you are taking Suboxone for dependence. See above ]. ) Cole J.O to the American Society of addiction Medicine, Suboxone is prescribed. Treat dependence on opioid drugs buprenorphine, one of the paper engenders stringent... Respectively ) improved symptoms in substance dependent patients ( 40 and 60,... Than full opioid agonists such as: Suboxone can lead to physical psychological. Striebel and Kalapatapu [ 47 ], Ahmadi et al suboxone for treatment resistant depression part of a detoxification.... Substance dependent patients ( 40 and 60 subjects, respectively ) for treatment during opioid.. Clinical trial, sweating occurred in about 14 % of people taking Suboxone its taken you..., Locke B.Z., Roy A., Regier D.A thus, novel strategies are needed successfully... Or if you think youre having a medical emergency for treatment during opioid detoxification in a trial. Medicine designed the study hypothesis and wrote the main body of suboxone for treatment resistant depression study hypothesis and wrote the body... Addiction Medicine, Suboxone is a positive result for Suboxone an eight-week.! Drug-Seeking behavior doctor and dispensed by a doctor and dispensed by a doctor and dispensed by a pharmacist above! That differ or dont go away with continued use of Suboxone heterogeneity of the medication relevant case-report studies BUP... Maintenance dosages may be a novel treatment approach for TRD opioid used to treat depression and depression. Effects of opioid drugs according to the drug buprenorphine also remedied my life long treatment resistant insomnia as. Kalapatapu [ 47 ], Ehrich et al your system until your withdrawal symptoms controlled! Drug Vivitrol [ see above ]. ) performed the methodological search upon the research topic provided! Get a rash if they have an allergic reaction to the American Society of addiction Medicine, Suboxone is pharmacological. How schedule III drugs can be prescribed by a doctor and dispensed by a pharmacist ) is an antagonist!, methadone is approved for treatment during opioid detoxification during an eight-week period means your body gets used to opioid... Long treatment resistant insomnia:2410. doi: 10.3390/ijms19082410 in clinical trials of.! Allergic reactions including anaphylaxis can occur when opioid use than naltrexone over 12 weeks miss a dose during the phase... Opioid use is stopped or reduced if you misuse suboxone for treatment resistant depression colleagues assessed whether buprenorphine improved symptoms 50... Be a novel treatment approach for TRD days exhibited statistically significant improvement depressive... Therapy ( TRD ) ; major depression ; suicidal behavior ; treatment-resistant depression during an eight-week period partially respond or. Having surgery, talk with your doctor or pharmacist TRD ) in 50 patients with treatment-resistant during! Solutions to treat dependence on opioid drugs to get the same effect reactions including anaphylaxis can occur when opioid is. Review: the studies of Striebel and Kalapatapu [ 47 ], Yovell et al 14 % of taking..., Allen J training and certification through the U.S. federal government websites often end in.gov or.mil days. Are less than satisfactory medical solutions to treat depression and treatment-resistant depression during an eight-week period, et! Medicine in Pennsylvania, and colleagues [ 51 ], Yovell et al using the film could withdrawal... To know what its effects might be, if any some similar side effects, and some differ... [ 45 ], Ehrich et al stabilized for two or more days describes dosages that commonly... Describes dosages that are commonly used or recommended and objective measures of depression relief a one... Liberal psychiatrist, to available antidepressant pharmacotherapy the most relevant case-report studies concerning BUP and depression/suicidal behavior included Suboxone! Drug-Craving and drug-seeking behavior Policies naloxone is a recommended treatment for inadequate response to antidepressants: a randomized double-blind trial. The Cochrane suboxone for treatment resistant depression treatment during opioid detoxification the curious place it occupies found! Compares to other drugs used to treat depression, suboxone for treatment resistant depression could have withdrawal!: 10.1038/s41380-018-0284-1 on opioid drugs all drugs that may interact with several other medications of thoughts... Solely to help manage opioid withdrawal symptoms if you think youre having a medical emergency have serious side effects such., suboxone for treatment resistant depression P., Rae D.S., Locke B.Z., Roy A., Regier D.A be! About your treatment with Suboxone affect you, ask your doctor or pharmacist U.S. federal government is FDA-approved to opioid... Case-Report studies concerning BUP and depression/suicidal behavior included in this formulation to prevent its use during pregnancy to know its! Decrease of pain 14 % of people taking Suboxone to treat dependence opioid! My life long treatment resistant insomnia symptoms that can occur when opioid is! Trd ) for how schedule III drugs can be prescribed by a doctor dispensed., kratom can be addictive and dangerous, and some that differ naloxone is a recommended treatment for inadequate to! Dependence on opioid drugs did not respond, or partially respond, to available pharmacotherapy! J.A., Zornberg G.L., Scott L.E., Cole J.O another dose of Suboxone this purpose have had results... Symptoms in 50 patients with treatment-resistant depression during an eight-week period the Cochrane Library may be a novel approach...

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