Scientific letter
Treatment of acute mania with methylphenidate: Therapeutic approach based on a new pathophysiological model
Tratamiento de la manía aguda con metilfenidato: propuesta terapéutica basada en un nuevo modelo fisiopatológico
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=> array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Treatment of acute mania with methylphenidate: Therapeutic approach based on a new pathophysiological model" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Sir:</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "93" "paginaFinal" => "94" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Pilar López-García, Ulrich Hegerl" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Pilar" "apellidos" => "López-García" "email" => array:1 [ 0 => "p.lopez@uam.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Ulrich" "apellidos" => "Hegerl" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Instituto de Investigación, Hospital Universitario de La Princesa, Madrid, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "CIBERSAM, Madrid, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de la manía aguda con metilfenidato: propuesta terapéutica basada en un nuevo modelo fisiopatológico" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The initial treatment for patients with acute mania represents a significant clinical challenge, given that treatments for mania symptom control usually take several days to start acting. Most treatments available for the manic phase of bipolar disorder are sedatives, to lower the hyperactivity and excitation that patients with mania present. However, recent observations<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> indicate that these symptoms may be the result of a self-regulating mechanism consisting of an increase in excitation and activity to compensate a deficit in vigilance or arousal. What is involved is a physiopathological model that proposes the existence of a state of brain hypoactivation in mania and that can open new therapeutic approaches.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The arousal regulation model has recently been proposed as a physiopathological mechanism that may be altered in affective disorders. The transition from the arousal state to that of sleep corresponds to different neurophysiological levels of vigilance, so various brain activity stages can be measured using electroencephalography (EEG). Regulating arousal levels implies an adaptive physiological mechanism that can adapt to an individual's biological needs and to environmental circumstances. For example, in situations of danger the organism raises the arousal level to face the situation, while vigilance drops in rest periods. In addition, continued states of increased arousal are often linked with the tendency to withdraw from external stimulation; in contrast, tired states can be associated with hyperactive behaviour as a self-regulating attempt to maintain arousal level. Based on this model, some vulnerable individuals present alterations in the self-regulating physiological arousal mechanisms, so states of brain hypoactivation or lowered arousal levels might lead to a clinical picture of mania. This unstable arousal regulation can have a pathogenic role in mania. Sleep deficits and other factors that destabilise arousal set off a self-regulating behavioural syndrome characterised by hyperactivity and increased speech and distractibility. In vulnerable individuals, the self-regulating mechanism could cancel out the physiological tendency to seek sleep, which can aggravate sleep deficits and increase instability in arousal regulation. In turn, this would trigger a vicious circle causing full-blown mania. This pathogenic concept provides an explanation for various aspects that are apparently paradoxical. First of all, in contrast to clinical observation of hyperactivity, evidence based on EEG data shows that patients with mania rapidly move towards low arousal level, frequently in the first seconds of the EEG record.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Secondly, the sleep deficit or life experiences that alter sleep-arousal regulation can trigger or worsen manic behaviour.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Finally, suspending substances that stabilise arousal (such as nicotine) can precipitate manic episodes.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">All these data suggest that psychostimulant drugs can be useful in treating some clinical conditions of mania. Likewise, observation of patients with attention deficit hyperactivity disorder (ADHD), a disorder with high comorbidity and wide overlaps in symptoms with bipolar disorder,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> also provides arguments in favour of using psychostimulants to treat mania: these drugs reduce attention deficits, sensation-seeking behaviour and hyperactivity in patients with ADHD<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>; methylphenidate improves sleep in children and adults with ADHD; psychostimulants in children with ADHD and additional manic symptoms are effective in reducing both the symptoms of ADHD itself and the manic symptoms.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In addition, the efficacy of psychostimulants in the initial treatment of acute mania has been confirmed: in some isolated cases, manic symptoms have improved rapidly and clearly after administering these drugs in adult manic patients with bipolar disorder.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8,9</span></a> A recent study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> demonstrated the efficacy of a psychostimulant, modafinil, in mania symptoms. In addition, this clinical improvement was associated with a stabilisation of vigilance.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Although psychostimulants have sometimes been associated with inducing mania,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> the turn to mania seldom occurs. Some studies<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> on children with bipolar disorder and ADHD found that using psychostimulants added to the treatment with a mood stabiliser not only improved the ADHD symptoms, it also improved those of mania. Furthermore, a systematic analysis performed by the US Food and Drug Administration<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> found low frequency of symptoms similar to mania in patients with ADHD treated with methylphenidate. Consequently, the risk of worsening mania seems low.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Using psychostimulants to control mania symptoms in bipolar disorder is a novel therapeutic approach with a physiopathological basis in the model of unstable vigilance regulation in affective disorders. To test the usefulness of this therapeutic proposal, which would mean a significant change in focus for bipolar disorder treatment, clinical assays with psychostimulants during mania stages are needed. The fact that methylphenidate acts very rapidly can facilitate early control of the symptoms of acute mania, which would be an advantage compared with other types of treatment currently available. We have now initiated an international multicentre clinical assay with academic institutions in Germany, Spain, Hungary, Belgium and Portugal to test this hypothesis in the clinical population.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: López-García P, Hegerl U. Tratamiento de la manía aguda con metilfenidato: propuesta terapéutica basada en un nuevo modelo fisiopatológico. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 2 | 6 |
| 2024 October | 32 | 30 | 62 |
| 2024 September | 13 | 30 | 43 |
| 2024 August | 37 | 38 | 75 |
| 2024 July | 19 | 15 | 34 |
| 2024 June | 29 | 17 | 46 |
| 2024 May | 20 | 14 | 34 |
| 2024 April | 21 | 14 | 35 |
| 2024 March | 19 | 19 | 38 |
| 2024 February | 13 | 17 | 30 |
| 2024 January | 21 | 23 | 44 |
| 2023 December | 18 | 41 | 59 |
| 2023 November | 27 | 22 | 49 |
| 2023 October | 38 | 47 | 85 |
| 2023 September | 48 | 28 | 76 |
| 2023 August | 11 | 25 | 36 |
| 2023 July | 13 | 26 | 39 |
| 2023 June | 26 | 15 | 41 |
| 2023 May | 41 | 10 | 51 |
| 2023 April | 42 | 7 | 49 |
| 2023 March | 24 | 9 | 33 |
| 2023 February | 15 | 2 | 17 |
| 2023 January | 19 | 6 | 25 |
| 2022 December | 13 | 4 | 17 |
| 2022 November | 17 | 6 | 23 |
| 2022 October | 18 | 7 | 25 |
| 2022 September | 26 | 16 | 42 |
| 2022 August | 19 | 10 | 29 |
| 2022 July | 9 | 7 | 16 |
| 2022 June | 19 | 9 | 28 |
| 2022 May | 10 | 11 | 21 |
| 2022 April | 25 | 5 | 30 |
| 2022 March | 49 | 14 | 63 |
| 2022 February | 38 | 3 | 41 |
| 2022 January | 51 | 5 | 56 |
| 2021 December | 32 | 14 | 46 |
| 2021 November | 21 | 18 | 39 |
| 2021 October | 32 | 10 | 42 |
| 2021 September | 30 | 13 | 43 |
| 2021 August | 64 | 12 | 76 |
| 2021 July | 41 | 6 | 47 |
| 2021 June | 45 | 15 | 60 |
| 2021 May | 42 | 10 | 52 |
| 2021 April | 113 | 55 | 168 |
| 2021 March | 108 | 9 | 117 |
| 2021 February | 61 | 16 | 77 |
| 2021 January | 36 | 12 | 48 |
| 2020 December | 27 | 11 | 38 |
| 2020 November | 22 | 12 | 34 |
| 2020 October | 18 | 6 | 24 |
| 2020 September | 20 | 8 | 28 |
| 2020 August | 25 | 10 | 35 |
| 2020 July | 22 | 12 | 34 |
| 2020 June | 31 | 5 | 36 |
| 2020 May | 23 | 10 | 33 |
| 2020 April | 19 | 1 | 20 |
| 2020 March | 10 | 3 | 13 |
| 2020 February | 16 | 7 | 23 |
| 2020 January | 20 | 3 | 23 |
| 2019 December | 21 | 11 | 32 |
| 2019 November | 7 | 9 | 16 |
| 2019 October | 13 | 3 | 16 |
| 2019 September | 13 | 8 | 21 |
| 2019 August | 21 | 3 | 24 |
| 2019 July | 24 | 25 | 49 |
| 2019 June | 51 | 12 | 63 |
| 2019 May | 126 | 19 | 145 |
| 2019 April | 41 | 15 | 56 |
| 2019 March | 12 | 7 | 19 |
| 2019 February | 19 | 4 | 23 |
| 2019 January | 24 | 5 | 29 |
| 2018 December | 31 | 0 | 31 |
| 2018 November | 43 | 6 | 49 |
| 2018 October | 17 | 0 | 17 |
| 2018 September | 38 | 7 | 45 |
| 2018 August | 25 | 1 | 26 |
| 2018 July | 22 | 1 | 23 |
| 2018 June | 11 | 2 | 13 |
| 2018 May | 15 | 1 | 16 |
| 2018 April | 47 | 3 | 50 |
| 2018 March | 11 | 4 | 15 |
| 2018 February | 4 | 3 | 7 |
| 2018 January | 6 | 0 | 6 |
| 2017 December | 9 | 3 | 12 |
| 2017 November | 7 | 0 | 7 |
| 2017 October | 13 | 2 | 15 |
| 2017 September | 12 | 2 | 14 |
| 2017 August | 10 | 6 | 16 |
| 2017 July | 16 | 6 | 22 |
| 2017 June | 14 | 7 | 21 |
| 2017 May | 18 | 6 | 24 |
| 2017 April | 13 | 3 | 16 |
| 2017 March | 9 | 3 | 12 |
| 2017 February | 15 | 2 | 17 |
| 2017 January | 8 | 1 | 9 |
| 2016 December | 14 | 4 | 18 |
| 2016 November | 23 | 3 | 26 |
| 2016 October | 25 | 1 | 26 |
| 2016 September | 20 | 12 | 32 |
| 2016 August | 16 | 3 | 19 |
| 2016 July | 21 | 2 | 23 |
| 2016 June | 26 | 10 | 36 |
| 2016 May | 27 | 8 | 35 |
| 2016 April | 12 | 13 | 25 |
| 2016 March | 23 | 9 | 32 |
| 2016 February | 19 | 9 | 28 |
| 2016 January | 24 | 20 | 44 |
| 2015 December | 13 | 10 | 23 |
| 2015 November | 13 | 7 | 20 |
| 2015 October | 24 | 10 | 34 |
| 2015 September | 14 | 4 | 18 |
| 2015 August | 13 | 4 | 17 |
| 2015 July | 10 | 5 | 15 |
| 2015 June | 7 | 6 | 13 |
| 2015 May | 9 | 7 | 16 |
| 2015 April | 14 | 11 | 25 |
| 2015 March | 20 | 5 | 25 |
| 2015 February | 15 | 5 | 20 |
| 2015 January | 13 | 3 | 16 |
| 2014 December | 37 | 9 | 46 |
| 2014 November | 23 | 7 | 30 |
| 2014 October | 35 | 3 | 38 |
| 2014 September | 28 | 4 | 32 |
| 2014 August | 27 | 5 | 32 |
| 2014 July | 21 | 6 | 27 |
| 2014 June | 13 | 7 | 20 |
| 2014 May | 20 | 3 | 23 |
| 2014 April | 15 | 6 | 21 |
| 2014 March | 13 | 5 | 18 |
| 2014 February | 10 | 2 | 12 |
| 2014 January | 20 | 6 | 26 |
| 2013 December | 26 | 4 | 30 |
| 2013 November | 18 | 4 | 22 |
| 2013 October | 21 | 4 | 25 |
| 2013 September | 32 | 7 | 39 |
| 2013 August | 37 | 5 | 42 |
| 2013 July | 39 | 13 | 52 |
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