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Osmotic-Release Oral System Methylphenidate Augmentation of Antidepressant Monotherapy in Major Depressive Disorder: Results of a Double-Blind, Randomized, Placebo-Controlled Trial
Abstract
Objective To evaluate the efficacy, safety, and tolerability of adjunctive osmotic-release oral system (OROS) methylphenidate in outpatients with major depressive disorder (MDD) receiving a stable oral antidepressant regimen. Method This multicenter, double-blind, randomized, placebo-controlled, parallel-group, 5-week trial enrolled 145 subjects who met DSM-IV-TR criteria for MDD and who had failed 1 to 3 previous antidepressant monotherapies (including current antidepressant) of adequate dose and duration. Augmentation therapy was initiated with 18 mg of OROS methylphenidate and increased to a maximum dose of 54 mg of OROS methylphenidate until an optimal dose was achieved. Efficacy scales included the Montgomery-Asberg Depression Rating Scale (MADRS), 7 atypical items from the 31-item Hamilton Rating Scale for Depression, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the CGI-Improvement scale (CGI-I), the Sex Effects scale, the Multidimensional Assessment of Fatigue (MAF) scale, and the Apathy Evaluation Scale (AES). Subjects were recruited at 17 community and academic centers across Canada. The study was conducted from June 8, 2005, to April 18, 2006. Results There was no statistically significant difference between the groups at endpoint on the MADRS. OROS methylphenidate was superior to placebo in improving apathy and fatigue as measured by the AES and the MAF. Statistically significant differences using mixed-model analysis were observed on the AES…
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“In support of the latter hypothesis, methylphenidate has been reported to be efficacious in reducing apathy in individuals with Alzheimer's disease (Rosenberg et al., 2013) and apathy and fatigue in individuals with MDD (Ravindran et al., 2008).”
From Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies (2016) · cites this paper as Ravindran et al., 2008
In the citing paper
“but they are generally consistent with published findings for psychostimulant (Patkar et al., 2006;Postolache et al., 1999;Ravindran et al., 2008) and modafinil augmentation studies for MDD (DeBattista et al., 2003;Dunlop et al., 2007;Fava et al., 2007) and with the conclusions of published meta-analyses (Candy et al., 2008;Fleurence et al., 2009).”
From Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies (2016) · cites this paper as Ravindran et al., 2008
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Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., Hasnain, M., Jollant, F., Levitt, A. J., MacQueen, G. M., et al. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716659417 · Cited by 1,181
“A few studies have addressed residual symptoms, such as fatigue or sexual dysfunction.(134,135) However, there is no consistent evidence to support specific adjunctive agents to target specific residual symptoms or side effects.”
BackgroundSelf-citationMalhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842
“Two randomised placebo controlled trials of augmentation with the stimulant methylphenidate have also failed to demonstrate efficacy (Patkar et al., 2006; Ravindran et al., 2008).”
BackgroundKennedy, S. H., Lam, R. W. M., Parikh, S. V., Patten, S. B., & Ravindran, A. V. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.06.043 · Cited by 529
Self-citationLam, R. W., Kennedy, S. H., Grigoriadis, S., McIntyre, R. S., Milev, R., Ramasubbu, R., Parikh, S. V., Patten, S. B., & Ravindran, A. V. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.06.041 · Cited by 431
“Two RCTs of augmentation with the CNS stimulant, methylphenidate, failed to detect differences in outcomes from placebo (Patkar et al., 2006; Ravindran et al., 2008) and a Cochrane systematic review found equivocal results for psychostimulants as augmentation to antidepressants (Candy et al.”
ResultSelf-citationLam, R. W. M., Kennedy, S. H., McIntyre, R. S., & Khullar, A. (2014) · The Canadian Journal of Psychiatry · doi:10.1177/070674371405901206 · Cited by 475
Self-citationTreatment-resistant depression: Definitions, review of the evidence, and algorithmic approach
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“Combination with psychostimulants Several negative studies indicate that methylphenidate is not reliably efficacious as an adjunct to conventional antidepressant therapy in adults with MDD (Ravindran et al., 2008; Patkar et al., 2006).”
BackgroundSexual Dysfunction, Depression, and the Impact of Antidepressants
Kennedy, S. H., & Rizvi, S. (2009) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31819c76e9 · Cited by 338
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The vigilance regulation model of affective disorders and ADHD
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“(2008), also failed to show an antidepressant effect of stimulants as add-on (Beck et al., 2010; Dunlop et al., 2007; Ravindran et al., 2008), with the exception of one small short-term trial with modafinil add-on (Abolfazli et al.”
BackgroundConnolly, K. R., & Thase, M. E. (2010) · Drugs · doi:10.2165/11587620-000000000-00000 · Cited by 468
“Another placebo-controlled trial of OROS -methylphenidate in 2008 similarly failed to find a significant difference in primary depression outcomes in a sample of 145 subjects with a history of one to three failed antidepressant treatments, although the stimulant group again had a numerically superior outcome.([58])”
Identifying and treating cognitive impairment in bipolar disorder
Goldberg, J. F., & Chengappa, K. R. (2009) · Bipolar Disorders · doi:10.1111/j.1399-5618.2009.00716.x · Cited by 180
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Self-citationPharmacological approaches to the challenge of treatment-resistant depression
Ionescu, D. F., Rosenbaum, J. F., & Alpert, J. E. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.2/dionescu · Cited by 229
Therapeutic options in treatment-resistant depression
Vieta, E., & Colom, F. (2011) · Annals of Medicine · doi:10.3109/07853890.2011.583675 · Cited by 101
Managing Partial Response or Nonresponse
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Dopamine, effort-based choice, and behavioral economics: basic and translational research.
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“…with these findings with animal models, human studies have shown that amphetamine and methylphenidate, and the atypical DA transport inhibitor modafinil, can have positive effects on motivational symptoms in depressed patients (Stotz et al., 1999; Lam et al., 2007; Ravindran et al., 2008).”
ResultPharmacological approaches in bipolar disorders and the impact on cognition: a critical overview
Dias, V. V., Balanzá‐Martinez, V., Soeiro‐de‐Souza, M. G., Moreno, R. A., Figueira, M. L., Machado‐Vieira, R., & Vieta, E. (2012) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2012.01910.x · Cited by 146
“Other agents include mifepristone (RU-486), a cortisol synthesis inhibitor, which was found to improve spatial working memory performance, verbal fluency, and spatial recognition memory in BD patients, as compared with placebo; however, no significant effect on working or verbal episodic memory was described (153).”
BackgroundThe Role of Dopamine in Symptoms and Treatment of Apathy in Alzheimer's Disease
Mitchell, R. A., Herrmann, N., & Lanctôt, K. L. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00161.x · Cited by 142
“Ravindran 2008 [138] Double-blind randomized controlled trial 145 patients with major depression taking an SSRI or Dual action agent antidepressant Methylphenidate OROS (18–54 mg/day) or placebo Improvement in symptoms of apathy (based on AES) in treatment group compared to placebo (P = 0.”
MethodResultGoss, A. J., Kaser, M., Costafreda, S. G., Sahakian, B. J., & Fu, C. H. Y. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13r08560 · Cited by 133
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“While this had the advantage of permitting direct quantitative comparisons across studies, it also limited the scope of the review by excluding additional studies on fatigue that did not meet these criteria, including studies of bupropion [62, 63], venlafaxine [64], levomilnacipran [65, 66] and osmotic release oral sy…”
Self-citationAdult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD
Binder, C., McIntosh, Kutcher, S., Levitt, Rosenbluth, & Fallu (2009) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s4720 · Cited by 110
Self-citationvan der Velden, P. G., Kleber, R. J., & Koenen, K. C. (2008) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2007.11.001 · Cited by 108
Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications
Lucido, M. J., Bekhbat, M., Goldsmith, D. R., Treadway, M. T., Haroon, E., Felger, J. C., & Miller, A. H. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000043 · Cited by 133
“However, in randomized trials in depression, augmentation with methylphenidate has not demonstrated a statistical benefit over standard therapy alone (Patkar et al., 2006; Michelson et al., 2007; Ravindran et al., 2008; Pary et al., 2015).”
BackgroundSalamone, J., Correa, M., Ferrigno, S. M., Yang, J.-H., Rotolo, R., & Presby, R. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015107 · Cited by 95
“In this context, it is interesting to note that amphetamine, methylphenidate, and modafinil have been reported to have positive effects on motivational symptoms in patients with depression (Stotz et al., 1999; Lam et al., 2007; Ravindran et al., 2008).”
BackgroundPharmacologic approaches to treatment resistant depression: Evidences and personal experience
Tundo, A., de Filippis, R., & Proietti, L. (2015) · World Journal of Psychiatry · doi:10.5498/wjp.v5.i3.330 · Cited by 94
Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: Current Management Perspectives
Atmaca, M. (2020) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s185757 · Cited by 89
“Ravindran et al reported that patients with majör depressive disorder who did not respond a variety of antidepressant agents including SSRIs did not also respond toosmotic controlled-release oral delivery systemmethylphenidateof 18 to54mgper day,without anyconsiderable change in the Montgomery–Asberg Depression Rating…”
BackgroundTreating to target in major depressive disorder: response to remission to functional recovery
McIntyre, R. S., Lee, Y. L., & Mansur, R. B. (2015) · CNS Spectrums · doi:10.1017/s1092852915000826 · Cited by 85
“The evidence for psychostimulants has been mixed, with most studies failing to provide robust and consistent signal of efficacy in reducing depressive symptoms.(48,49) Similar to psychostimulants, modafinil has not been able to provide reproducible efficacy in MDD, but has demonstrated improvement in symptoms/dimensio…”
ResultPharmacologic approaches to treatment resistant depression: a re-examination for the modern era
Philip, N. S., Carpenter, L. L., Tyrka, A. R., & Price, L. H. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656561003614781 · Cited by 76
“Another trial with extended release methylphenidate replicated these findings, although improvement was seen in fatigue and apathy [89].”
ResultPharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines
Taylor, R. W., Marwood, L., Oprea, E., DeAngel, V., Mather, S., Valentini, B., Zahn, R., Young, A. H., & Cleare, A. J. (2020) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa033 · Cited by 76
The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis
McIntyre, R. S., Lee, Y., Zhou, A. J., Rosenblat, J. D., Peters, E. M., Lam, R. W., Kennedy, S. H., Rong, C., & Jerrell, J. M. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000723 · Cited by 75
Self-citationAugmentation strategies for treatment-resistant depression
Carvalho, A. F., Machado, J. R., & Cavalcante, J. L. (2008) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32831be9ef · Cited by 78
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A Preliminary Study of fMRI-Guided rTMS in the Treatment of Generalized Anxiety Disorder
Bystritsky, A., Kerwin, L. E., & Feusner, J. D. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08l04641 · Cited by 43
Steiner, H., & Waes, V. V. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.10.001 · Cited by 58
“as augmentation therapy in major depressive disorder (e.g., Nelson, 2007; Ishii et al., 2008; Ravindran et al., 2008), as”
Emerging antidepressants to treat major depressive disorder
Block, S. G., & Nemeroff, C. B. (2014) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2014.09.001 · Cited by 55
“However, OROS methylphenidate was more effective than placebo in improving apathy and fatigue (Ravindran et al., 2008).”
BackgroundDo the old psychostimulant drugs have a role in managing treatment‐resistant depression?
Parker, G., & Brotchie, H. (2010) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2009.01434.x · Cited by 50
A Review of Antidepressant Therapy in Primary Care
Kennedy, S. H. (2013) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.12r01420 · Cited by 41
Self-citationStimulants for depression: On the up and up?
Malhi, G. S., Byrow, Y., Bassett, D., Boyce, P., Hopwood, M., Lyndon, W., Mulder, R., Porter, R., Singh, A., & Murray, G. (2016) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867416634208 · Cited by 46
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“…with psychostimulants might be associated with moderate or marked improvement in depression, or at least improvement in some domains related to depression, such as fatigue and apathy (Mendonca et al. 2007; Ravindran et al. 2008; McIntyre et al. 2013; Trivedi et al. 2013; Sinita and Coghill 2014).”
BackgroundChallenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics
de Sousa, R. T., V. Zanetti, M., R. Brunoni, A., & Machado-Vieira, R. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150630173522 · Cited by 43
“However, in one of these studies methylphenidate significantly improved fatigue and apathy [80].”
BackgroundThe use of stimulant medications for non-core aspects of ADHD and in other disorders
Sinita, E., & Coghill, D. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.06.014 · Cited by 43
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“…treatments are also employed in depression, for example as augmentation therapy in major depressive disorder (e.g. Nelson, 2007; Ishii et al., 2008; Ravindran et al., 2008), as acceleration treatment with SSRIs (e.g. Lavretsky et al., 2003), or to treat sexual dysfunction (e.g. Csoka et al., 2008).”
Dopaminergic agents in the treatment of bipolar depression: a systematic review and meta-analysis
Szmulewicz, A. G., Angriman, F., Samamé, C., Ferraris, A., Vigo, D., & Strejilevich, S. A. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12712 · Cited by 37
Antidepressant drug development: Focus on triple monoamine reuptake inhibition
Lane, R. M. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881114553252 · Cited by 41
“Although adjunctive stimulants may accelerate response and show significant efficacy on individual symptoms—such as fatigue and apathy—a compelling body of evidence of additional overall efficacy at the end of acute treatment is lacking (Ravindran et al., 2008).”
BackgroundA Systematic Review of Studies Using the Multidimensional Assessment of Fatigue Scale
Belza, B., Miyawaki, C. E., Liu, M.-H., Aree-Ue, S., Fessel, M., Minott, K., & Zhang, X. (2018) · Journal of Nursing Measurement · doi:10.1891/1061-3749.26.1.36 · Cited by 32
Hutson, P. H., Tarazi, F. I., Madhoo, M., Slawecki, C., & Patkar, A. A. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.03.005 · Cited by 31
“However, multiple studies did not report significant improvements in depressive symptoms following augmentation with methylphenidate (Postolache et al., 1999; Patkar et al., 2006; Ravindran et al., 2008) or the wake-promoting agent modafinil (DeBattista et al.”
BackgroundQuantifying motivational deficits and apathy: A review of the literature
Weiser, M., & Garibaldi, G. M. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.08.018 · Cited by 31
“…difference (MCID) in AES score, although changes in mean scores have indicated a sensitivity to treatment effects in AD, PD and MDD patients (Padala et al., 2010; Lam et al., 2012; Drapier et al., 2008; Marangell et al., 2002; Ravindran et al., 2008; Raskin et al., 2012; Lenze et al., 2012).”
The use of dopaminergic and stimulant drugs for the treatment of depression.
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Incentive salience: novel treatment strategies for major depression
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“Two recent studies on adding stimulants to SSRIs showed improvement for specific symptoms of fatigue and apathy.(30,31) However, controlled studies have failed to demonstrate significant changes in response or remission.”
Abbasowa, L., Kessing, L. V., & Vinberg, M. (2013) · Nordic Journal of Psychiatry · doi:10.3109/08039488.2012.752035 · Cited by 27
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“Similarly, Ravindran and colleagues demonstrated a non-significant difference in MADRS scores between patients treated with OROS-methylphenidate (18–54 mg/day) in addition to a standard antidepressant regimen compared to patients receiving a placebo and standard antidepressant over a period of 5 weeks (Ravindran et al…”
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“Two RCTs of augmentation with methylphenidate failed to detect differences in outcomes compared with placebo [44, 45].”
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“SSRIs are first-line treatments for major depressive disorder (MDD) and are also helpful to treat anxiety disorders, obsessive compulsive disorder and others.”
BackgroundInfluentialAttention-Deficit/Hyperactivity Disorder and Comorbid Subsyndromal Depression
Golubchik, P., Kodesh, A., & Weizman, A. (2013) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e31829eb204 · Cited by 22
“It seems that ADHD symptoms are less responsive to MPH in patients with relatively high CDRS scores (possible depression) and that those patients may be candidates for selective serotonin reuptake inhibitor treatment as a supplement for MPH.”
BackgroundInfluentialEfficacy of off-label augmentation in unipolar depression: A systematic review of the evidence
Kleeblatt, J., Betzler, F., Kilarski, L. L., Bschor, T., & Köhler, S. (2017) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.03.003 · Cited by 25
“However, a statistically significant improvement on specific symptoms such as apathy and fatigue, as well as a good tolerability were observed (Ravindran et al., 2008).”
InfluentialRichards, C., McIntyre, R. S., Weisler, R., Sambunaris, A., Brawman-Mintzer, O., Gao, J., Geibel, B., Dauphin, M., & Madhoo, M. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.07.006 · Cited by 20
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Kluge, M., Hegerl, U., Sander, C., Dietzel, J., Mergl, R., Bitter, I., Demyttenaere, K., Gusmão, R. M., González-Pinto, A. M., Pérez, V., et al. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-71 · Cited by 16
Use of atypical antipsychotics for treatment-resistant major depressive disorder
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“Augmentation strategies can involve adding lithium [9,17,18], triiodothyronine [18], buspirone [14], pindolol [19], omega-3 fatty acids [20], dopaminergic agents [21, 22 ], folates, or S-adenosyl methionine [23,24] to an antidepressant treatment regimen.”
BackgroundWake-Promoting Pharmacotherapy for Psychiatric Disorders
Dell’Osso, B. M., Dobrea, C., Cremaschi, L., Arici, C., & Altamura, A. C. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0524-2 · Cited by 18
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Life-long consequences of juvenile exposure to psychotropic drugs on brain and behavior
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“…and MDD (Rushton and Whitmire, 2001; Safer et al., 2003), which occurs with up to 40% prevalence in pediatric ADHD populations (Waxmonsky, 2003; Spencer, 2006), as well as in the treatment of other conditions (e.g., Lavretsky et al., 2003; Nelson, 2007; Csoka et al., 2008; Ravindran et al., 2008).”
BackgroundYrondi, A., Javelot, H., Nobile, B., Boudieu, L., Aouizerate, B., Llorca, P., Charpeaud, T., Bennabi, D., Antoine Lefrere, A., & Samalin, L. (2024) · L Encéphale · doi:10.1016/j.encep.2023.11.029 · Cited by 24
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Yang, H., Sinicropi-Yao, L., Chuzi, S. E., Youn, S. J., Clain, A. J., Baer, L., Chen, Y., McGrath, P. J., D, M. F. M., & Papakostas, G. I. (2010) · Annals of General Psychiatry · doi:10.1186/1744-859x-9-10 · Cited by 16
Fluoxetine Potentiates Oral Methylphenidate-Induced Gene Regulation in the Rat Striatum
Moon, C., Marion, M., Thanos, P. K., & Steiner, H. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02466-y · Cited by 18
Beverley, J. A., Piekarski, C., Waes, V. V., & Steiner, H. (2014) · Basal Ganglia · doi:10.1016/j.baga.2014.10.001 · Cited by 15
Therapeutic Armamentarium for Treating Depression
Howland, R. H. (2010) · Postgraduate Medicine · doi:10.3810/pgm.2010.07.2176 · Cited by 14
Richards, C., Iosifescu, D. V., Mago, R., Sarkis, E., Reynolds, J., Geibel, B., & Dauphin, M. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117722998 · Cited by 14
“…with the published literature describing the effects of stimulant augmentation for MDD in general (Candy et al., 2008; Fleurence et al., 2009; Patkar et al., 2006; Postolache et al., 1999; Ravindran et al., 2008) and with the phase 3 studies of LDX augmentation for MDD (Richards et al., 2016).”
BackgroundCurrent Trends in Identifying Rapidly Acting Treatments for Depression
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Ontiveros, J. A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82568
“Controlled studies evaluating placebo versus methylphenidate have been negative despite its regular use [114].”
Yohn, S. E., Reynolds, S., Tripodi, G., Correa, M., & Salamone, J. D. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.12.039 · Cited by 13
The Role of Stimulants in Late-Life Depression
Nelson, J. C. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15030356 · Cited by 13
Hrabak, M., Moon, C. J., Bolaños-Guzmán, C. A., & Steiner, H. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03688-y · Cited by 9
“Furthermore, methylphenidate plus SSRI combinations are used for a number of other purposes, including to accelerate or augment the effects of SSRIs in the treatment of depression (e.g., [17–20]) or others (e.g., [21]).”
Lamoureux, L., Beverley, J. A., Marinelli, M., & Steiner, H. (2023) · Addiction Neuroscience · doi:10.1016/j.addicn.2023.100131 · Cited by 12
“MP+SSRI concomitant treatments are also indicated for a number of other conditions in adults, including augmentation therapy in major depressive disorder [15–17], augmentation of partial response to stimulants [18], reversal of stimulant-induced insomnia [19] and others.”
BackgroundGiacobbe, P., Rakita, U., Lam, R. W. M., Milev, R. V., Kennedy, S. H., & McIntyre, R. S. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.09.041 · Cited by 12
Self-citationPharmacological treatment approaches to difficult‐to‐treat depression
Chan, H., Mitchell, P. B., Loo, C. K. A., & Harvey, S. B. (2013) · The Medical Journal of Australia · doi:10.5694/mja12.10495 · Cited by 12
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Lithium, Thyroid Hormones and Further Augmentation Strategies in Treatment‐resistant Depression
Haußmann, R., & Bauer, M. (2013) · Wiley eBooks · doi:10.1002/9781118556719.ch6 · Cited by 7
Pharmacological treatment approaches to difficult-to-treat depression
Chan, H., Mitchell, P. B., Loo, C. K. A., & Harvey, S. B. (2012) · The Medical Journal of Australia · doi:10.5694/mjao12.10495 · Cited by 2
Janela, D., Jerónimo, J., Rema, J., Telles‐Correia, D., & Novais, F. (2023) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-023-00307-4 · Cited by 7
“Thirteen studies were included [1, 6, 8, 9, 15, 17, 19, 23, 26, 28, 29, 32] (Table 1).”
InfluentialLee, W., Sheehan, C., Chye, R., Chang, S., Loo, C. K. A., Draper, B., Agar, M. R., & Currow, D. C. (2021) · BMJ Open · doi:10.1136/bmjopen-2021-052312 · Cited by 7
Central nervous system stimulants in recreational and medical use
Dodd, S., Ospina-Pinillos, L., & Markowitz, J. S. (2025) · CNS Spectrums · doi:10.1017/s1092852925100357 · Cited by 4
“26 38 Agents like methylphenidate and modafinil have shown benefits in improving energy and mood in selected patients.”
Hrabak, M., Ahmed, R., Soriano, M. G., Powell, A., Thanos, P. K., & Steiner, H. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04569-8 · Cited by 4
“Moreover, methylphenidate plus SSRI combinations are also used for other purposes, including augmentation of SSRI effects in the treatment of depression (e.g., [9–12]), or other conditions (e.g., [13]).”
Dépression résistante : les autres stratégies thérapeutiques
Saba, G., Nieto, I., Bation, R., Allaïli, N., Bennabi, D., Molière, F., Richieri, R. M., Holtzmann, J., Bubrovszky, M., Camus, V., et al. (2016) · La Presse Médicale · doi:10.1016/j.lpm.2016.02.005 · Cited by 3
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The association between suspected long–COVID and stimulant prescribing in the United States
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Adult ADHD: Questioning Diagnosis and Treatment in a Patient with Multiple Psychiatric Comorbidities
Chu, R., Rosic, T., & Samaan, Z. (2017) · Case Reports in Psychiatry · doi:10.1155/2017/1364894 · Cited by 3
“However, this may simply be a result of stimulants reducing fatigue and apathy, rather than depressive symptoms [32, 33].”
BackgroundMadhusoodanan, S., & Goia, D. (2014) · doi:10.2217/cpr.14.32 · Cited by 3
Gauthier, L., Drui, G., Debatisse, J., Saga, Y., Millot, M., Martinez, E., Météreau, É., Portier, K., Tobler, P. N., Tremblay, L., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03794-6 · Cited by 3
“For instance, in MDD patients, the combined use of MPH and SSRIs does not affect depression severity compared to SSRI monotherapy, but can signi fi cantly improve fatigue and apathy [73, 74].”
Steiner, H., Hrabak, M., & Bolaños‐Guzmán, C. A. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106344 · Cited by 2
Pharmacological Management of Treatment‐Resistant Unipolar Depression
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Psychostimulants and treatment resistant depression
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Tackling Partial Response to Depression Treatment
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Pharmakologische Behandlungsmöglichkeiten bei therapieresistenter Depression
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“Die Subanalyse zeigte Vorteile einer Augmentation mit Methylphenidat in Bezug auf die Faktoren „Apathie“ und „Müdigkeit“ (47, 48).”
BackgroundRichards, C., Iosifescu, D. V., Mago, R., Sarkis, E. H., Geibel, B., Dauphin, M., McIntyre, R. S., Weisler, R. H., Brawman‐Mintzer, O., Gu, J., et al. (2018) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000897 · Cited by 1
Metadata
- Authors
- Ravindran, A. V., Kennedy, S. H., O'Donovan, M. C., Fallu, A., Camacho, F., & Binder, C. E.
- Affiliations
- University of Toronto (CA)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2008-01-15
- Volume
- 69
- Issue
- 1
- Pages
- 87-94
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W1987459299
- Cited by
- 119
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 8 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 14 · 2014: 13 · 2013: 13 · 2012: 7
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- osmotic-release oral system, OROS methylphenidate, major depressive disorder, antidepressant-resistant depression, apathy, fatigue, tolerability, adverse effects
- MeSH terms
- Adult, Central Nervous System Stimulants, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Drug Synergism, Drug Therapy, Combination, Female, Humans, Male, Methylphenidate, Middle Aged, Severity of Illness Index, Diagnostic and Statistical Manual of Mental Disorders
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