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Title: Nonbiological aspects of drug-resistant depression


Depression is one of the most common psychiatric disorders among thegeneral population. It is often characterized by a recurrent or chronic course, and itimposesa considerable burden on both the patients and their families. Depressive disordersoften diminish patients’ ability to get good education and find gainful employment,leading to significant impairment. According to the WHO rapport published in 2001depression in the course of bipolar disorder will be the leading cause of disabilityworldwide in 2020.Approximately 30% of patients diagnosed with depression do not achieveimprovement following the initial antidepressant trial. About half of this subgroupwill not respond adequately to the second antidepressant trial either. High ratio ofrecurrence (80-85%) contributes to unsatisfactory effectiveness of the availabletreatments. There are two groups of patients: one in which many differentantidepressive drugs were admitted and there were no satisfactory improvement ofmental state and the second group where the treatment brings improvement but aftera longer period of time.Low remission rates among substantial proportion of chronicallydepressed patients contribute to a number of adversities, such as: higher psychiatrichospitalization ratio, higher burden of medical condition, and trend towardsworsening of depressive symptoms over. Those patients have shorter survival time,their family and social relationships are disturbed, and they become less efficient inwork, leading to early abandonment of occupation. The percentage of committedsuicides in this group of depressive patients is significantly higher than the drugresistantpatients with no improvement.The aim of this study was to evaluate relationships between drugresistanceand various nonfarmacological aspects that contribute to effectiveness ofantidepressant treatment. Accordingly, severity of the depressive and anxietysymptoms, during the episode we analyzed, as well as level of anxiety as a part ofpersonality structure. Presence of bipolar features, style of parental care in thefamily, personality traits, level of stress before and after depressive episode, familialmechanisms, and some of the features of patients’ bipolar disorder course wereanalyzed. Beck Depression Inventory (BDI), Hamilton Depression Rating Scale(HDRS), Mood Disorder Questionnaire (MDQ), State-Trait AnxietyInventory(STAI, X1,X2), Social Readjustment Rating Scale (SRRS), ParentalBonding Instrument (PBI), Familial Questionnaire – Bipersonal RelationshipQuestionaire, Self-Esteem Inventory, Formal Characteristic of Behavior –Temperament Inventory and data derived from clinical history were used. ; 169 subjects were enrolled into the study:1) 65 patients with major depression or recurrent depressive disorder who metcriteria of drug-resistance according to Helmchenfs definition;2) 54 patients with major depression or recurrent depressive disorder whoachieved .50% reduction in symptoms severity3) 50 healthy volunteers as a control group.The groups did not differ significantly in terms of the most importantsociodemografic data; age, sex ratio, level of education. 6 investigational hypotheseshave been put forward. Two of them have been confirmed, 2 have been partlyconfirmed, and 2 have not been confirmed at all.The data gathered from BDI and HDRS have reached the severity of majordepression. In terms of BDI scores, drug-resistant and drug-non-resistant subjectsdid not differ in terms of the severity of depressive symptoms at baseline. Patients inboth groups experienced in their own opinion very similar level of severity ofdepressive symptoms, however the higher arithmetic mean was observed in groupwith not sufficient response. In terms of HDRS scores, subjects with drug-resistantdepression presented with statistically more severe depressive symptoms, suggestingthat severity of depression at baseline might be a predictor of drug-resistance.High trait anxiety (as indicated by the two subscales of STAI inventory)was bound to higher likelihood of drug-resistance. Level of anxiety as a state and aswell as a feature exceeded mean value of 60 points in the group of patients withdrug-resistant depression, as opposed to depressive patients who responded well tothe therapy. In the group of non-drug-resistant patients arithmetic mean withstandard deviation did not exceed the value of 60 points, and the difference betweenthis group and the group of drug-resistant patients was statistically significant foranxiety as a state as well as feature.An Assessment of bipolar spectrum features showed a statisticallysignificant difference between groups of drug-resistant and drug-non- resistantpatients. In the latter group more subjects scored positively on MDQ, as opposed tothe hypothesis of connection between drug-resistance and undiagnosed features ofbipolarity.In all groups, the most common type of relationship with mothers (analyzedby the PBI questionnaire) was the one described as .control without a feelingh. Intwo depressive groups this kind of bond was present in over 60% of patients, and inthe control group it was observed only in 40% of volunteers. The characteristics ofrelationship with fathers the results were similar, however in two depressive groupsa bond described as .control without a feelingh was less prevalent (about 50%). Adistinct type of childhood relationship withparents was not related to treatment-resistance of future depressive disorders.Results from examination of different aspects of family functioning reveal atype of discomfort that is present in families with a member suffering from ; depression. The type of depression course has no significant influence oneffectiveness of pharmacotherapy. Basing on statistical differences discomfort as afeature more frequently applies to the group of patients that responded sufficiently totreatment. It might be related with a better adaptation ofdrug-resistant patients' families to a longer period of depression and creatingadaptive mechanisms.In terms of Formal Characteristics of Behavior – Temperament Inventoryscores, subjects with drug-resistance presented a specific structure of individualpersonality traits. 75% of drug-resistant subjects were described as the highestemotional reactivity, the lowest resistance, activity, and liveliness population. Thispattern of personality traits among drug-resistant patient explore party characteristicthat is described as coherent structure indicating small possibilities of processingstimulation.Drug-resistance had a higher correlation with divorces, longer priorepisodes, course of depression with less frequent episodes without hospitalizationthan it was expected. Suicidal thoughts and attempts were more frequently observedin drug-resistant group.This trail provides additional data on pharmacotherapyeffectiveness predictors. This study also do not concentrate on biological factors thatregard receptor response to drugs, but tries to find explanation in the structure ofhuman's psyche.The trail’s results imply the necessity of identification and supervision ofthose patients that did not respond sufficiently to the initial antidepressant trial andverify the psychological and pharmacological procedures that have been used.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

psychiatria ; psychologia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.


Dominika Dudek

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Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

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Feb 7, 2020

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Jul 12, 2013

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Edition name Date
ZB-118397 Feb 7, 2020


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