The effect of interpersonal psychotherapy on quality of life among breast cancer patients with common mental health disorder: a randomized control trial at Tikur Anbessa Specialized Hospital

To determine the effect of interpersonal psychotherapy on anxiety, depression, and quality of life among breast cancer patients with mental health disorders at Tikur Anbessa Specialized Hospital, Ethiopia. A two-arm parallel randomized controlled trial study was conducted among 114 (n = 57 intervention, and n = 57 control group) breast cancer patients with common mental health disorder at the oncology center of Tikur Anbessa Specialized Hospital. The hospital anxiety and depression measurement scale was used to assess depression and anxiety disorder and a 30-item quality of life questionnaire was used to assess the quality of life. General linear model analysis was done, confounding factors were controlled, and p < 0.05 was used to declare statistical significance. Patients in the intervention group showed a significant improvement in the anxiety (coefficient − 3.68; 95% CI − 5.67, − 1.69; p < 0.001), depression (coefficient − 3.22; 95% CI − 4.7, − 1.69; p < 0.001), physical functioning (coefficient 10.55; 95% CI 3.13, 17.98; p = 0.006), health-related quality of life (coefficient 21.85; 95% CI 14.1, 29.59; p < 0.001), insomnia (coefficient − 19.56; 95% CI − 31.87, − 7.25; p = 0.002), and fatigue (coefficient − 11.37; 95% CI − 21.49, − 1.24; p = 0.028) respectively. The adapted Ethiopian version of interpersonal psychotherapy had improved anxiety, depression, and some domains of health-related quality of life. Hence, health programmers should consider incorporating it as a treatment option in oncology centers. PACTR202011629348967 granted on 20 November 2020 which was retrospectively registered.


Introduction
Breast cancer has become the leading cause of global cancer incidence in 2020, with an estimated 2.3 million new cases, representing 11.7% of all cancer cases and the fifth leading cause of cancer deaths (685,000) worldwide [1]. In Africa, breast cancer causes an estimated 168,690 cases and 74,072 deaths [2]. In Ethiopia, breast cancer is the commonest cancer type [3], which accounts for 34% of all female cancer cases, according to the Addis Ababa cancer registry survey [4].
Depression and anxiety are the forms of common mental health disorders experienced by cancer patients [5]. Both disorders are serious medical illness that negatively affects people's feelings, emotions, cognition, behavior, and physical condition [6]. Depression experiences in cancer patients have been significantly related to reduced quality of life [7]. Anxiety is common psychological distress in cancer patients that leads to autonomous overactivity and anxious behavior [8].
Depression and anxiety are among the psychiatric illnesses that can be treated [9]. Quality of life (QOL) is one of the common patient-reported outcome measures [10] and it is strongly related to psychological distress in a way that when psychological distress gets treated, quality of life improves [11]. Psychotherapy is a collection of interrelated approaches intended to improve social, physical, behavioral, psychological wellness, and mental health [12]. In minimizing the intensity of somatic and psychic symptoms, psychotherapy has become very important [13].
The use of interpersonal psychotherapy as an acute and chronic treatment is effective in cancer patients with major depressive disorders [14]. There are studies conducted on the relationship between cancer and mental health disorders in Ethiopia [15,16]. However, to the best level of our knowledge, the effect of interpersonal psychotherapy on anxiety, depression, and quality of life among breast cancer patients was not investigated yet. Therefore, this study aimed to determine the effect of interpersonal psychotherapy on anxiety, depression, and quality of life among breast cancer patients with mental health disorders in Tikur Anbessa Specialized Hospital, Ethiopia.

Methods and materials
A two-arm parallel randomized control trial was conducted at the oncology center of Tikur Anbessa Specialized Hospital (TASH). Participants were individually assigned into intervention and control groups at a 1:1 ratio. Interpersonal psychotherapy intervention was given for the intervention group and no intervention was provided for the control group. Participants in both groups received their routine care and treatment (radiotherapy, chemotherapy, and hormonal therapy). The study was conducted at the oncology center of TASH, Addis Ababa, Ethiopia, from January to August 2019. TASH is the biggest specialized hospital and the only cancer diagnostic and treatment center in Ethiopia with both radiotherapy and chemotherapy treatment options [17].

Participants
Adult breast cancer patients aged ≥ 18 years, diagnosed with anxiety and depression using the hospital anxiety and depression measurement scale was included in the study. Participants with severe physical illness, severe mental illness, functionally impairing substance abuse, acute suicidal attempt, patients who were on any sort of psychotherapy, and patients who are on psychiatric medication were excluded from the study.

Randomization
All the patients were allocated to one of two groups and the Microsoft Excel 2016 random sequence generator was used for the sequential assignment into the two groups. Nurses who were not involved in the study randomized participants 1:1 to either the intervention or control group.

Intervention
Four trained professional therapists delivered the interpersonal psychotherapy treatment as per the adapted interpersonal psychotherapy for Ethiopian version (IPT-E) guideline [18]. The baseline information of socio-demographic, economic, clinical characteristics, and quality of life were obtained after consent.
As per the IPT-E guideline, the therapeutic process consists of the beginning phase, middle phase, and that of the final phase. IPT-E session consists of a total of 4-8 sessions. However, in this study, the intervention involved 4-6 therapy sessions.

Beginning phase
The therapist asked the questions that help patients to understand their problems, symptoms, explanatory model, and psychosocial supports. The therapeutic relationship, provision of feedback, and identification of IPT problem areas (loss, change, or disagreements) were established for the focus of the middle phase sessions.

Middle phase
The therapist was working through aspects of underlying interpersonal problems and helping patients to connect with supports. Even though it was recommended to focus on one problem area, the therapist sometimes extended the therapeutic focus to other areas when it was believed to be saliently linked to current distress.

Final phase
The patient's efforts and progress were reviewed; contingency plans were made in case of symptoms worsen. Furthermore, old losses were processed and symptoms that might be mistaken for a re-occurrence of the original symptoms that brought the patient to treatment. The therapists met the patients every week for 30-60 min per session.

Anxiety and depression
The level of depression and anxiety, as calculated by the established Hospital Anxiety and Depression Measurement Scale (HADS), were the primary outcome measures [19]. The items were rated on a four-point Likert scale ranging from 0 to 3, with 0 and 21 as the minimum and maximum scores for each subscale, respectively. Anxiety or depression sub-scales with sub-scores ranging from 0 to 7 are considered normal, 8 to 10 are considered cause for concern, and 11 to 21 are considered probable cases of anxiety or depression [20]. The HADS measurement scale was interpreted as follows: 0 to 7 represents normal, 8 to 10 represents mild, 11 to 14 represents moderate, and 15 to 21 represents severe.

Quality of life
The secondary outcome measure of this study was the QOL. It was tested using the Amharic version of the EORTC QLQ-C30, which was found to be accurate and valid for evaluating QOL among cancer patients [21]. The questionnaire has 30 items with three scales and 15 different domains. The three scales used were functional, symptom scale, and general health status as a separate scale: domains such as physical, role, cognitive, emotional, and social functioning under functional scale whereas dyspnea, pain, fatigue, insomnia, appetite loss, nausea/vomiting, constipation, diarrhea, and financial difficulties under symptom scale, and general health status as a separate scale. The scoring was done according to the QOL questionnaire-C30 manual [22].

Sample size justification
Overall, 400 breast cancer patients attended the oncology center during the study period. Of these, 124 patients were eligible for the study and we randomly assigned 62 patients to the intervention group and 62 patients to the control group.

Statistical analysis
The collected data were coded, checked for its consistency, and completeness up to the end of the data collection period. The Epi DATA version 4.4.2.1 software was used for data entry and the entered data were exported to the Minitab version 18 software for windows. Descriptive statistics of categorical variables were presented using frequency and percentages and a chi-square test was used to determine differences between the intervention and control groups. Univariate and multivariate regression was computed before fitting the domains and the independent variables into the analysis of covariance (ANCOVA). Additionally, a general linear model (ANCOVA) was used to measure the effect of IPT-E on QOL after controlling the effect of covariates. A per-protocol analysis was used and a p value < 0.05 was used to declare the statistical significance.

Results
During the study period, 400 patients were receiving routine service at the oncology center of TASH; of these, 132 patients were eligible for the study. Of the total 132 patients, 8 patients were refused to participate in the study. Finally, 124 participants were consented to participate in the study and randomized into the intervention and control groups. Of the 124 randomized into intervention and control groups, 10 participants were lost to follow-up. Overall, the data of 114 participants were included in the final analysis ( Fig. 1) yielded a 91.9% response rate (Table 1).

Quality of life of the patients
IPT-E improved physical functioning, decreased insomnia, fatigue, and improved health-related QOL. IPT-E was found to be associated with an increased physical functioning in the intervention group (p = 0.006, coefficient 10.55; 95% CI 3.13, 17.98) compared to the control group and participant's age was found to affect the post-intervention physical functioning with (p = 0.02; 95% CI − 0.796, − 0.071). Baseline depression was found to be associated with post-intervention physical functioning with (p = 0.02; 95% CI − 2.45, − 0.216).
After the intervention, there was a decrease in fatigue scores. The breast cancer stage significantly affects fatigue; the patient's being stage IV highly increased the post-intervention fatigue score (p = 0.015; 95% CI 5.7, 51.21). The intervention had improved the insomnia score with (p = 0.02; 95% CI − 31.87, − 7.25). Being in the highest quintile negatively affects insomnia with (p = 0.04) ( Table 3).

Discussion
In this study, IPT was found to be effective in reducing anxiety and depression. This was consistent with the previous studies [23][24][25]. This finding was consistent with one meta-analysis and a randomized controlled trial study, which indicates the usefulness of psychological intervention for cancer survivors with depression and anxiety [23,24]. Similarly, a randomized controlled study conducted in France found a significant reduction in anxiety and depression in the intervention group [25]. Our analysis showed a significant negative association between post-intervention anxiety score and the patient being in the highest quintile. Similarly, a study done in India indicated that those patients with low monthly income and less financial support tend to be more anxious than the other contrasts [26]. This is because cancer treatment imposes unbearable costs which cause frustration among patients. In our study, we found a positive association between post-intervention anxiety score, radiotherapy, and mastectomy treatment. Similarly, another study found that radiotherapy leads to increased emotional distress, anxiety, and depression [27]. The potential reason for this may be that patients tend to worry about the critical side effects that they may experience due to the radiotherapy.
Patients also tend to frustrate about the likelihood of radiotherapy damaging other organs or giving them other forms of cancer. Similarly, breast cancer patients who had mastectomy experienced emotional disturbance [28]. Females with mastectomy suffered emotional disturbance. This might be due to the fact that the breast is a sign of womanhood in many cultures, and its absence is believed to affect sexual attraction from the opposite sex that in turn will inflict a huge emotional burden. In this study, physical functioning of patients in the IPT group was improved significantly when compared with that of the control group. This was in line with other randomized controlled trial studies [29][30][31]. Age and depression were negatively associated with physical functioning. This was consistent with the study conducted in Germany [32]. This could be due to the high risk of reduced physical functioning and the natural physiological phase of aging among older patients. There is a significant association between depression and physical functioning. In line with our finding another study showed that, by reducing depressive symptoms, there could be an improvement in physical functioning [33]. This may be because depression results in some physical symptoms such as tiredness, weight loss, and loss of appetite, and such physical signs may affect physical functioning.
Insomnia was significantly affected by the therapy administered; similarly, another study found an improved self-rated sleep parameter among breast cancer patients [34], and reduced incidence of sleep disturbances among patients [35]. Similarly, another study that implemented 12 weeks of mindfulness-based stress reduction technique found improved sleep quality in patients with breast cancer [36] which implied that sleep difficulties can be alleviated by psychotherapeutic intervention. In our study, patients that encountered sleep disturbance were offered sleep hygiene that in turn helped them to alleviate the problem. Fatigue is also another symptom scale that was improved by IPT. This finding was consistent with another study that determined the effect of mindfulness-based stress reduction technique on reducing fatigue and other study conducted on investigating the effect of supportive-expressive group discussion on quality of life, in cancer survivors [37,38] which they found a decreased fatigue score among the intervention group. Our result showed that being stage IV highly predicted fatigue. The possible explanation for this could be that as the stage of the cancer increases physical deterioration becomes inevitable, thereby, patients also started to experience severe pain and fatigue.
The health-related quality of life of breast cancer patients was improved by IPT. Similarly, other studies that used different kinds of therapy techniques have found an improved health-related quality of life [31,38]. Our result revealed that there was a significant association between the patient being in the highest quintile and health-related quality of life. In line with this finding, a study showed that socio-economic status has an impact on health-related quality of life in which the potential explanation could be that levels of income are related to nutrition, accommodation, and access to health care, all of which are important to the HRQOL of a person [39,40].

Limitations of the study
We measured the post-intervention outcome 2 weeks after the final psycho-therapy session, which might influence our outcome. In addition, the study used the patients' response for outcome assessment so it is somewhat subjective. Additionally, we were unable to control the therapist-to-therapist difference that could influence our outcome.

Strengths of the study
We used a validated tool and a strong study design to determine the depression, anxiety, and quality of life of the study participants. The inclusion of patients diagnosed with only one type of cancer also ensures the homogeneity of the groups, thus ensuring that the finding is representative.

Conclusions
In this study, interpersonal psychotherapy for Ethiopian use affected anxiety, depression, and quality of life of breast cancer patients with a common mental health disorder. Hence, health programmers may consider incorporating it as a treatment outcome.