Pharmacogenetics of escitalopram and mental adaptation to cancer in palliative care: report of 18 cases.

AIMS AND BACKGROUND: In palliative care, few data are available on the diagnosis and treatment of mood disorders and of difficulties of mental adaptation to cancer for patients in the advanced phases of the disease. SSRI antidepressants are the treatment of choice; the 5-HTTLPR genetic polymorphism of the serotonin transporter (SERT) has been shown in psychiatry to significantly determine the therapeutic response and the incidence of adverse effects. The aim of the present investigation has been therefore to examine the effects of the SSRI antidepressant escitalopram, also considering 5-HTTLPR, on depression, anxiety and mental adaptation to cancer in palliative care. METHODS AND STUDY DESIGN: Eighteen consecutive depressed patients with different forms of advanced cancer admitted to the Hospice Ass 6 of S. Vito al Tagliamento (Pordenone, Italy) were genotyped for the "s" and "l" variants of 5-HTTLPR and were treated with escitalopram. Their response after two weeks of treatment was psychometrically evaluated. RESULTS: Treatment with escitalopram significantly decreased anxiety scores on the Hospital Anxiety and Depression Scale (HADS) (P = 0.006) as well as anxious preoccupation (P = 0.007) and hopelessness-helplessness (P = 0.017) scores on the Mini Mental Adjustment to Cancer (Mini-MAC) scale. When patients were stratified by SERT genotype, HADS anxiety was significantly decreased in patients carrying the "s/s" and "s/l" variants (P = 0.024), whereas those with an "l/l" genotype displayed a significant reduction of Mini-MAC anxious preoccupation (P = 0.018). CONCLUSIONS: The results of this study indicate that the use of SSRI antidepressants is effective in the palliative care of cancer patients, and their action affects not only depression but also the patients' mental adaptation to the disease. These results encourage further examination of these drugs in a larger cohort of patients. The significant contribution of pharmacogenetics indicates the possibility of personalized treatment with SSRIs in palliative care.

Serotonin transporter 5-HTTLPR polymorphism and response to citalopram in terminally ill cancer patients: report of twenty-one cases.

The aim of this study was to examine the effects of the SSRI antidepressant drug citalopram on anxiety, depression and mental adjustment to cancer in terminally ill cancer patients, considering also the 5-HTTLPR genetic polymorphism. A group of twenty-one consecutive patients admitted to the hospice of the Casa di Cura Pineta del Carso (Trieste, Italy) with different types of advanced cancer, who were clinically judged to require treatment with an antidepressive drug, was treated with citalopram for two weeks. The response was determined and related to 5-HTTLPR. Citalopram significantly reduced the scores on the depression and anxiety subscales of the Hospital Anxiety and Depression Scale (HADS). When the effects of citalopram were analyzed in relation to the 5-HTTLPR polymorphism, the HADS depression score was significantly decreased only in patients with the "l/l" allelic variant of the serotonin transporter conferring high functional activity, while the score of the Mini-MAC fatalism scale was significantly increased in patients carrying at least one "s" allele. These preliminary findings seem to indicate that two weeks of treatment with citalopram are effective in reducing depressive symptoms in terminally ill cancer patients. Moreover, the effects of citalopram on fatalism as a strategy of mental adaptation to cancer, and on depressive symptoms depend on the allelic variants of the 5-HTTLPR genotype of the patients. These results seem to encourage the examination of a larger patient sample and of different treatment schedules, as well as a more thorough characterization of fatalism as a coping strategy in cancer patients.

5-HTTLPR polymorphism of serotonin transporter and effects of sertraline in terminally ill cancer patients: report of eleven cases.

Depression is difficult to detect in cancer patients, though its determination offers an opportunity to relieve patients' suffering in palliative care. Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for mood disorders, but they show a highly variable response. The short allelic variants "s/s" and "s/l" of the 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene has been consistently associated with a poorer response to SSRIs. The aim of this study has therefore been to examine depression, anxiety and mental adaptation to cancer in terminally ill and depressed cancer patients, in relation to treatment with sertraline and to the 5-HTTLPR genetic polymorphism. Eleven consecutive depressed patients with different forms of advanced cancer who were admitted to the Hospice of the Casa di Cura "Pineta del Carso" (Trieste, Italy) were treated with sertraline for two weeks and their response was determined and related to 5-HTTLPR. Sertraline significantly reduced the average depression and anxiety subscale scores of HADS, as well as the scores of the subscales of Mini-MAC. When the effects of sertraline were analyzed in relation to the 5-HTTLPR polymorphism, only patients with the "l/l" allelic variant had significantly lower scores of HADS anxiety, Mini-MAC hopelessness-helplessness and anxious preoccupation, and a higher score for the fighting spirit of Mini-MAC; the depression score was significantly reduced in patients with both allelic variants. These data indicate that sertraline is effective after two weeks of treatment in terminally ill cancer patients, acting not only on depression but also on anxiety and mental adaptation to cancer. Moreover, the effect of sertraline significantly depended on the genetic polymorphism of the serotonin transporter, being more pronounced in patients carrying the "l/l" genetic variant; these findings seem to encourage the examination of a larger sample of patients.

An early structured psychoeducational intervention in patients with breast cancer: results from a feasibility study.

BACKGROUND: Although the incidence of breast cancer in Italy is high, like in most Western countries, the role of psychosocial support in disease management and outcome is incompletely understood. A structured psychoeducational group intervention has been shown by Fawzy (J Psychosom Res. 1999, 45:191-200) to increase psychological well-being and natural killer immunological reactivity in patients with melanoma, with decreased relapse rate and prolonged survival time. OBJECTIVE: The aims of the present study were to assess the feasibility of Fawzy's intervention by preliminary evaluation of its usefulness on a sample of women with early-stage breast cancer. METHODS: Psychological reaction to the disease and its possible modification by the psychoeducational treatment were determined with the Mini-Mental Adjustment to Cancer scale at the time of study recruitment and at the end of the intervention. RESULTS: A total of 29 patients participated in the study. Rate of participation and adherence to the intervention were 83% and 100%, respectively. A significant reduction in anxious preoccupation was observed in treated patients, whereas the other coping strategies identified by the Mini-Mental Adjustment to Cancer scale were not significantly modified. CONCLUSION: The results support the feasibility of the intervention. In particular, the reduction in anxious preoccupation, characterizing the early phase of adaptation to breast cancer, may be the target for psychosocial intervention including specific nursing contributions. IMPLICATIONS FOR PRACTICE: The results obtained encourage investigating in more depth and with adequate methodology the role of psychoeducational group support for patients with early-stage breast cancer. In particular, they suggest that more attention should be given to the early phase, which follows the communication of cancer diagnosis and precedes the beginning of chemotherapy, which seems to be characterized by anxious preoccupation. A further indication resulting from the study and development of psychoeducational groups for patients with cancer is the opportunity to include cancer nursing among the topics that are addressed during psychoeducational group meetings because it seems to have been neglected in the available studies despite its evident relevance in cancer care.

Psychological response to cancer: role of 5-HTTLPR genetic polymorphism of serotonin transporter.

BACKGROUND: 5-HTTLPR genetic polymorphism of serotonin transporter (SERT) and stressful life events facilitate depression. The aim of this investigation was therefore to determine the correlations between SERT polymorphism and mental adjustment to cancer. PATIENTS AND METHODS: Breast cancer patients early after surgery, and subjects with various advanced tumours were recruited, evaluated using the Mini Mental Adjustment to Cancer Scale and Hospital Anxiety and Depression Scale (HADS), and genotyped. RESULTS: In early breast cancer patients (n=53), hopelessness-helplessness (HH) and anxious preoccupation (AP) significantly correlated with depression and anxiety; avoidance (AV) correlated with anxiety. Advanced cancer patients (n=73) displayed similar correlations, and a negative correlation of HADS depression with fighting spirit (FS) and AV. The stratification for 5-HTTLPR showed that early breast cancer carriers of the L/L variant displayed a significant correlation between HH and depression. CONCLUSION: Among early breast cancer patients, a specific set, characterized by their 5-HTTLPR variant, display differential correlations between HH and depression, with possible implications for treatment options.