Changes in dream experience in relation with antidepressant escitalopram treatment in depressed female patients: a preliminary study

Studio sulla variazione dell’esperienza soggettiva del sogno in pazienti depressi
in corso di trattamento antidepressivo


ADELE QUARTINI1, ANNALISA ANASTASIA2, FRANCESCO SAVERIO BERSANI1,3,
CLAUDIA MELCORE1,3, GABRIELLA ALBANO1, CHIARA COLLETTI2, GIUSEPPE VALERIANI1,3,
GIUSEPPE BERSANI
1
E-mail: giuseppe.bersani@uniroma1.it

1Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome
2Department of Neuroscience and Behaviour, Section of Psychiatry, Federico II University of Naples
3Department of Neurology and Psychiatry, Sapienza University of Rome

RIASSUNTO. Introduzione. Sleep disturbances have long been considered as a cardinal symptom of endogenous depression and dreams in depressed patients usually differ from those of healthy people. The aim of the present study was to investigate dream subjective experiences and their modifications in relation to clinical response in a group of escitalopram-treated depressed patients. Methods. Twenty-seven female patients meeting DSM-IV-TR criteria for Major Depressive Disorder (MDD) and starting SSRI therapy were included in the study. Data about psychopathological status and dreaming subjective experiences were collected at baseline (T0), 4 weeks after the beginning of the treatment (T1) and after further 4 weeks of therapy (T2). Results. At T0 dream experience was impaired and negatively toned. Concomitantly with the decrease of symptoms severity, the 8-week escitalopram treatment yielded to significant improvements in the recall of both quantity and quality of dreams; those patients whit lower clinical benefits kept on reporting impaired dream experiences. Discussion. The results of the present study evidence how the changes in some specific dreaming characteristics, such as the subjective recall of dream activity, the dream recall quality, the dream emotional content and the dream complexity represent reliable markers of the effectiveness of antidepressant therapy.

KEY WORDS: depression, dream, sleep disturbances, psychopharmacology, escitalopram.


RIASSUNTO. Introduzione. Le anomalie del sonno REM nei pazienti depressi sono state ampiamente studiate e documentate. L’effetto del trattamento farmacologico antidepressivo si traduce nella riduzione di questa fase del sonno. L’esperienza dell’attività onirica nei pazienti depressi varia nel corso della terapia antidepressiva. Metodi. Sono stati inclusi nello studio 40 pazienti affetti da disturbo depressivo che necessitavano di trattamento farmacologico. Attraverso la somministrazione di questionari, ideati per l’analisi dell’esperienza soggettiva del sogno, sono state esplorate le seguenti variabili: quantità del sonno, quantità dei sogni, percezione del momento della notte di maggiore attività onirica, colorito emotivo dei sogni, qualità del ricordo dei sogni e loro complessità. Tali variabili sono state messe in relazione all’andamento della sintomatologia depressiva, valutata attraverso la Montgomery-Asberg Depression Rating Scale (MADRS). La MADRS e i questionari sono stati somministrati nel corso della prima visita (T0), e dopo 4 e 8 settimane di trattamento farmacologico (rispettivamente T1 e T2). Risultati. Parallelamente alla durata del trattamento antidepressivo, i pazienti hanno riportato un aumento della propria attività onirica (T0-T2: p=0,001), una variazione in senso positivo del colorito emotivo (T0-T1: p=0,003; T0-T2: p<0,001), un ricordo più chiaro (T0-T2: p=0,001) e una riduzione della complessità dei sogni (T0-T2: p=0,008). Conclusioni. Esistono variazioni dell’esperienza soggettiva del sogno nel corso del trattamento farmacologico antidepressivo. I pazienti riferiscono un aumento dell’attività onirica, un colorito emotivo meno negativo, un ricordo del sogno più chiaro, una minore complessità dei contenuti. Sebbene nel corso del trattamento un maggior numero di pazienti riferisca un momento di maggiore attività onirica prima del risveglio, tale dato non è risultato essere statisticamente significativo.

PAROLE CHIAVE: fase REM, attività onirica, disturbo depressivo, disturbi del sonno, psicofarmacologia, escitalopram.

INTRODUCTION
Sleep disturbances have long been considered as a cardinal symptom of endogenous depression. Objectively, polysomnographic studies of depressed patients evidenced that the internal sleep organization is impaired with reduced latency of the first REM sleep episode associated to increased density of REM sleep, a percentage reduction of the total length of deep Slow Wave Sleep (SWS) and an increase in night awakenings1-3.
Consistently with the abnormalities of sleep organization, dreams in patients with depression usually differ from those of healthy people. During depression, dreams have been reported to be shorter and less frequently remembered10. Their temporal perspective is generally restricted, with a preponderance of elements pertaining to the past; the setting is usually known and the dream characters are mostly family members11-14.
Common depressive themes, such as loss, death, separation have been showed to be prevalent in a number of studies15,16; in addition, some authors reported a high frequency of dreams with unpleasant contents, labelled “masochistic”, in which the dreamer was the recipient of rejection, disappointment, humiliation, or similar unpleasant experiences6,7,17,18.
Several studies showed that antidepressant pharmacological treatments were associated with increased dream recall frequency5,19-22 and with positive changes in dream emotional content12-18. However, contradictory data are present on the topic: some studies reported a decrease of dream recall frequency under tricyclic antidepressants21,22, phenelzine20, and SSRIs20 and unchanged or increased negative dream emotions in patients completely recovered from their depressive episodes5,23.
In this context, the aim of the present study was to investigate dream subjective experiences and their modifications in relation to clinical response in a group of escitalopram-treated depressed patients. Among the antidepressant drugs, escitalopram was chosen as it is the most selective SSRI24. To minimize variability due to gender differences, only female subjects have been included in the study.
METHODS
Twenty-seven female patients meeting DSM-IV TR criteria for Major Depressive Disorder (MDD) and starting SSRI therapy were included in the study. Patients were recruited at the outpatient psychiatric clinic of the A. Fiorini University Hospital, Sapienza University of Rome. All participants gave written informed consent and underwent an extended clinical interview by a fully certified consultant psychiatrist.
Subjects with any of the following were excluded: history of psychiatric disorders other than MDD or neurological disorders; lifetime substance abuse; antidepressant pharmacological treatment before the beginning of the study or concomitant use of additional medications.
Clinical data of patients were collected at baseline (T0), 4 weeks after the beginning of the treatment (T1) and after further 4 weeks of therapy (T2).
MDD severity was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI). The dream experiences were assessed through two specific questionnaires: the Subjective Experience of Dream questionnaire 1 (SED 1) at T0, that investigated the dream experience in the 4 weeks before T0, and the Subjective Experience of Dream questionnaire 2 (SED 2) at T1 and T2, that investigated the changes in dream experience between T0, T1, and T2. The two questionnaires have been specifically designed by our research team25 to explore the following dream parameters: subjective recall of dream activity (increased, unchanged, decreased); period of the night with recall of maximum dream activity (throughout the night, just after falling asleep, before awakening), recall of dream quality (clear, confused); dream emotional content (positive, neutral/variable, negative), and dream complexity (increased, unchanged, decreased).
Statistical analyses
Statistical analysis was performed using SPSS V16 (SPSS Inc., Chicago, IL, USA). Crosstabs and χ2 test were carried out to assess changes over the course of treatment in the different dream parameters. Repeated-Measures ANCOVAs with time as within-participant factor and age as covariate were carried out to assess clinical changes (MADRS and BDI total score). MANCOVA, yet covarying for age, was finally used to compare MADRS and BDI total scores according to the different patients’ dream characteristics (Bonferroni correction applied). The significant threshold was set at p≤.05.
RESULTS
Over the course of treatment, χ2 test revealed a significant enhance in the number of patients reporting an increased subjective dream activity [T0-T2, χ2(1)=12.79, p<.001; T1-T2, χ2(1)=5.08, p=.024], a clear dream recall quality [T0-T2, χ2(1)=6.13, p=.013], a positive dream emotional content [T0-T2 and T1-T2, χ2(1)=4.42, p=.036], and a reduced dream complexity [T0-T2, χ2(1)=5.59, p=.018]. A significant enhance was also found in the number of patients reporting as period of sleep with maximum dream activity the one just before awakening [T0-T2, χ2(1)=6.31, p=.012] (Table 1). Over the course of treatment, repeated-measures ANCOVAs showed a significant improvement in both the MADRS and BDI scores [MADRS, F (2,50)=6.87, p=.002; BDI (Greenhouse-Geisser correction), F (2,50)=5.74, p=.012]. At T2, MANCOVA revealed a significant effect of dreaming on both the MADRS and BDI scores [subjective dream activity, Pillai’s Trace, F (4,46)=4.56, p=.003; dream emotional content, Pillai’s Trace, F (4,46)=4.99, p=.002; and dream complexity, Pillai’s Trace, F(4,46)=3.95, p=.008]. Separate univariate ANCOVAs specifically revealed higher MADRS and BDI scores in patients kept on reporting a decreased subjective dream activity [MADRS, F(2,23)=9.82, p=.001; post-hoc pairwise comparisons: MADRS decreased-increased, 21.75±9.74 vs 8.14±4.80, p=.001; MADRS decreased-unchanged, 21.75±9.74 vs 6.89±5.77, p=.001. BDI, F(2,23)=11.13, p<.0001, post-hoc pairwise comparisons: BDI decreased-increased, 20.25±7.89 vs 6.86±3.86, p<.0001; BDI decreased-unchanged, 20.25±7.89 vs 7.78±6.16, p=.001], a negative dream emotional content [MADRS, F(2,23)=16.36, p<.0001, post-hoc pairwise comparisons: MADRS negative-positive, 29.50±3.53 vs 8.00±5.34, p<.0001; MADRS negative-neutral/variable, 29.50±3.53 vs 8.23±5.48, p<.0001. BDI, F(2,23)=11.15, p<.0001, post-hoc pairwise comparisons: BDI negative-positive, 26.00±7.07 vs 7.37±3.56, p=.001; BDI negative-neutral/variable, 26.00±7.07 vs 8.00±5.66, p<.0001], and an increased dream complexity [MADRS, F(2,23)=9.35, p=.001; post-hoc pairwise comparisons: MADRS increased-decreased, 20.67±10.26 vs 5.55±5.32, p=.001; MADRS increased-unchanged, 20.67±10.26 vs 10.07±6.45, p=.008. BDI, F(2,23)=4.17, p=.028; post-hoc pairwise comparisons: BDI increased-decreased, 17.00±12.49 vs 7.55±5.96, p=.028; BDI increased-unchanged, 17.00±12.49 vs 8.53±5.72, p=.042] (Table 2). No significant differences were found in the MADRS and BDI scores according to the remaining patients’ dream characteristics (Table 2).






DISCUSSION
Biorhythm distrurbances are common in depression as well as in other psychiatirc disorders26-28. The results of the present study seem to confirm earlier findings of an impaired dream experience in patients with depression.
For what concerns the dreaming assessment at T0, the difficulty in remembering dreams, already found in patients with depression in many previous studies5-8, is supported by the subjective feeling of a decreased dream activity reported by the majority of patients. In relation to dream emotional content, the results are consistent with previous studies8,29: before treatment, approximately 50% of patients were not able to identify a predominant dream emotion, whilst the other 50% prevalently experienced negative emotional content and unpleasant mood. The increased dreams’ complexity reported by the majority of patients and generally described as greater plot articulation of dreams and/or as dreams with enhanced number of bizarre elements, finally agree with the study of Kramer12 that found in the dreams of depressed patients a lower plausibility compared to a group of organic patients.
Remarkable changes in several dream parameters occurred after the beginning of antidepressant drug therapy.
Concomitantly with the decrease of depressive symptoms severity, the 8-week escitalopram treatment yielded to a significant improvement in the recall of both quantity and quality of dreams and, noteworthy, those patients whit lower clinical benefits kept on reporting impaired dream experiences. Specifically, MADRS and BDI scores remained high in those patients who kept on reporting reduced dream activity, negative dream emotional contents and increased dream complexity. Consistently with these findings, an enhancement of dreaming was previously noted during treatment with SSRIs fluoxetine 5,30 and citalopram31.
The reported increased dream activity following the therapy with escitalopram may appear paradoxical in relation to the wide literature data indicating a reduction of REM sleep duration during antidepressant treatment. A possible explication may be that a significant proportion of dreams also occurs in non-REM sleep32-38. Moreover, patients on antidepressant treatment often show a longer duration of sleep with delayed awakening respect to pretreatment period; since REM activity is more intense during the last part of the sleep, the increased recall of dreams could be mainly related to the recall of this last portion of REM activity4. In addition, a cognitive improvement following recovery from depression might be hypothesized to lead to an amelioration in the memory of dreams39.
The results of the study also indicated that patients on escitalopram treatment showed more clear recall of dream quality, less complex and more emotionally vivid dreams; these data confirm previous findings reported by the majority of authors29,40-43.
It is known that the study of sleep and circadian functions may help physicians in monitoring the progression of mood disorders4,44-51; the results of the present study evidence how the changes in some specific dreaming characteristics, such as the subjective recall of dream activity, the dream recall quality, the dream emotional content and the dream complexity represent reliable markers of the effectiveness of antidepressant therapy such as that with escitalopram. The easiness with which dream experience alterations can be explored during a clinical interview and the relative precocity with which such alterations appear along antidepressant treatment could make them potential valuable clinical markers.
Further investigations carried out on larger samples as well as in double-blind placebo-controlled designs are needed to better clarify the role of dreaming in depression and even in the prediction of remission from depression.
REFERENCES
 1. Boivin DB. Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders. J Psychiatry Neurosci 2000; 25: 446-58.
 2. Aguglia E, Biggio G, Signorelli MS, Mencacci C. Steering Commitee on behalf of the STIMA-D Investigators. Italina Study on Depressive Disorders (STudio Italiano MAlattia Depressiva, or STIMA-D): a nationawide snapshot of the status of treatment for major depression. Pharmacopsychiatry 20014; 47: 105-10.
 3. Biondi M, Bersani FS, Valentini M. The Italian edition of DSM-5. Riv Psichiatr 2014; 49: 57-60.
 4. Bersani FS, Iannitelli A, Pacitti F, Bersani G. Sleep and biorythm disturbances in schizophrenia, mood and anxiety disorders: a review. Riv Psichiatr 2012; 47: 365-75.
 5. Armitage R, Rochlen A, Fitch T, Trivedi M, Rush J. Dream recall and major depression: a preliminary report. Dreaming 1995; 5: 189-98.
 6. Beck AT, Ward CH. Dream and depressed patient. Arch Gen Psychiatry 1961; 5: 66-71.
 7. Cartwright RD. “Masochism” in dreaming and its relation to depression. Dreaming 1992; 3: 79-84.
 8. Riemann D, Löw H, Schredl M, Wiegand M, Dippel B, Berger M. Investigations of morning and laboratory dream recall and content in depressive patients during baseline conditions and under antidepressive treatment with trimipramine. Psychiatr J Univ Ott 1990; 15: 93-9.
 9. Salviati M, Bersani FS, Terlizzi S, et al. Tinnitus: clinical experience of the psychosomatic connection. Neuropsychiatr Dis Treat 2014; 10: 267-75.
10. Tirassa P, Iannitelli A, Sornelli F, et al. Daily serum and salivary BDNF levels correlate with morning-evening personality type in women an are affected by light therapy. Riv Psichiatr 2012; 47: 527-34.
11. Barrett D, Loeffler M. Comparison of dream content of depressed vs. non-depressed dreamers. Psychol Rep 1992; 70: 403-6.
12. Kramer M, Baldridge BJ, Whitman RM, Ornstein PH, Smith PC. An exploration of the manifest dream in schizophrenic and depressed patients. Dis Nerv Syst 1969; 30: 126-30.
13. Macrì F, Minichino A, Campi S, et al. Chronic conversion somatic disorder: a case report. Recenti Prog Med 2013; 104: 70-2.
14. Fonzi L, Matteucci G, Bersani G. Laughter and depression: hypothesis of pathogenic and therapeutic correlation. Riv Psichiatr 2010; 45: 1-6.
15. Kupfer DJ. REM latency: a psychobiologic marker for primary depressive disease. Biol Psychiatry 1976; 11: 159-74.
16. Nejad AG, Sanatinia RZ, Yousofi K. Dream contents in patients with major depressive disorder. Can J Psychiatry 2004; 49: 866-7.
17. Kramer M, Trinder J, Whitman RM, Baldridge BJ. The incidence of “masochistic dreams” in the night collected dreams of depressed subjects. Psychophysiology 1969; 6: 250.
18. Costantini A, Picardi A, Brunetti S, et al. Italian version of Demoralization Scale: a validation study. Riv Psichiatr 2013; 48: 234-9.
19. Landolt HP, Raimo EB, Schnierow BJ, Kelsoe R, Rapaport MH, Gillin JC. Sleep and sleep electroencephalogram in depressed patients treated with phenelzine. Arch Gen Psychiatry 2001; 58: 268-76.
20. Pace-Schott EF, Gersh T, Silvestri R, Stickgold R, Salzman C, Hobson JA. SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects. J Sleep Res 2001; 10: 129-42.
21. Schredl M, Mathias B, Dieter R. The effect of trimipramine on dream recall and dream emotions in depressive outpatients. Psychiatry Res 2009; 167: 279-86.
22. Whitman RM, Pierce CM, Mass JW, Baldridge BJ. Drugs and dreams II: imipramine and prochlorperazine. Compr Psychiatry 1961; 2: 219-26.
23. Hauri P. Dreams in patients remitted from reactive depression. J Abnorm Psychol 1976; 85: 1-10.
24. Kirino E. Escitalopram for the management of major depressive disorder: a review of its efficacy, safety, and patient acceptability. Patient Prefer Adherence 2012; 6: 853-61.
25. Fonzi L, Moscariello MM, Matteucci G, Pucci D, Bersani G. Changes in subjective dream experience and response to antidepressant treatment. Italian Journal of Psychopathology 2006; 12: 171-7.
26. Bersani FS, Iannitelli A, Pacitti F, Bersani G. Sleep and biorythm disturbances in schizophrenia, mood and anxiety disorders: a review. Riv Psichiatr 2012; 47: 365-75.
27. Bersani G, Mameli M, Garavini A, Pancheri P, Nordio M. Reduction of night/day difference in melatonin blood levels as a possible disease-related index in schizoprenia. Neuro Endocrinol Lett 2003; 24: 181-4.
28. Bersani G, Iannitelli A, Massoni E, et al. Ultradian variation of nerve growth factor plasma levels in healthy and schizophrenic subjects. Int J Immunopathol Pharmacol 2004; 17: 367-72.
29. Bollea, E, Carbonetti, P, Donini G, Marrucci M, Piccione M, Vella G. Attività onirica dei depressi. Arch Psicol Neurol Psichiatr 1978; 39: 473-501.
30. Pace-Schott EF, Hobson JA, Stickgold R. The fluoxetine mediated increase in NREM eye movements can be detected in the home setting using the Nightcap. Sleep Res 1994; 23: 459.
31. Koponen H, Lepola U, Leiononen E, Jokinen R, Penttinen J, Turtonen J. Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study. Acta Psychiatr Scand 1997; 96: 343-6.
32. Antrobus J. REM and NREM sleep reports: comparison of word frequencies by cognitive classes. Psychophysiology 1983; 20, 562-8.
33. Cavallero C, Foulkes D, Hollifield M, Rebecca T. Memory sources of REM and NREM dreams. Sleep 1990; 13: 449-55.
34. Foulkes D. Dream reports from different stages of sleep. J Abnorm Soc Psychol 1962; 65: 14-25.
35. Nielsen TA. Mentation in REM and NREM sleep: a review and possible reconciliation of two models. Behav Brain Sci 2000; 23: 851-66.
36. Oudiette G, Dealberto MJ, Uguccioni G, et al. Dreaming without REM sleep. Conscious Cogn 2012; 21: 1129-40.
37. Suzuki H, Uchiyama M, Tagaya H, et al. Dreaming during non-rapid eye movement sleep in the absence of prior rapid eye movement sleep. Sleep 2004; 27: 1486-90.
38. Bersani FS, Biondi M. Historical recurrences in psychiatry: somatic therapies. Riv Psichiatr 2012; 47: 1-4.
39. Herrera-Guzmán I, Gudayol-Ferré E, Herrera-Abarca JE, et al. Major Depressive Disorder in recovery and neuropsychological functioning: effects of selective serotonin reuptake inhibitor and dual inhibitor depression treatments on residual cognitive deficits in patients with Major Depressive Disorder in recovery. J Affect Disord 2010; 123: 341-50.
40. Cartwright RD, Lloyd S, Knight S, Trenholme I. Broken dreams: a study of the effects of divorce and depression on dream content. Psychiatry 1984; 47: 251-4.
41. Kramer M, Whitman RM, Baldridge BJ, Ornstein PH. Drugs and dreams: III. The effects of imipramine on the dreams of the depressed. Am J Psychiatry 1968; 124: 1385-92.
42. Riemann D, Berger M, Voderholzer U. Sleep and depression: results from psychobiological studies. Biol Psychol 2001; 57: 67-103.
43. Schredl M, Engelhardt H. Dreaming and psychopathology: dream recall and dream content of psychiatric inpatients. Sleep Hypn 2001; 3: 44-54.
44. Bersani G, Bersani FS, Prinzivalli E, et al. Premorbid circadian profile of patients with major depression and panic disorder. Riv Psichiatr 2012; 47: 407-12.
45. Bersani G, Liberati D, Rasa A, et al. Premorbid sleep, appetite, energy, and cognitive circadian profile in patients with depressive disorders. Eur Psychiatry 2010; 25: 461-4.
46. Bersani G, Garavini A. Melatonin add-on in manic patients with treatment resistant insomnia. Prog Neuropsychopharmacol Biol Psychiatry 2000; 24: 185-91.
47. Bersani FS, Minichino A, Enticott PG, et al. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry 2013; 28: 30-9.
48. Bersani G, Meco G, Denaro A, et al. l-Acetylcarnitine in dysthymic disorder in elderly patients: A double-blind, multicenter, controlled randomized study vs. fluoxetine. Eur Neuropsychopharmacol 2013; 2: 1219-25.
49. Moscariello MM, Ratti F, Quartini A, Forcén FE, Munuera JN, Bersani G. Presenza di elementi dissociativi in pazienti con disturbi dell’umore e disturbi d’ansia. Riv Psichiatr 2010, 45: 234-43.
50. Fonzi L, Matteucci G, Bersani G. Riso e depressione: ipotesi di rapporto patogenetico e terapeutico. Riv Psichiatr 2010; 45: 1-16.
51. Bersani FS, Girardi N, Sanna L, et al. Deep transcranial magnetic stimulation for treatment-resistant bipolar depression: a case report of acute and maintenance efficacy. Neurocase 2013; 19: 451-7.