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.

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.

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.

Pain treatment with high-dose, controlled-release oxycodone: an Italian perspective.

OBJECTIVE: To investigate the possible role and tolerability of high-dose (>160 mg/day) oxycodone controlled release (CR) for the treatment of cancer and non-cancer pain. DESIGN: 227 patients with cancer or non-cancer pain were enrolled in an open-label, multi-center, Italian study in order to assess the adequacy of their existing pain management (using a numerical rating scale [NRS]) and the possible benefit high-dose oxycodone CR may offer patients experiencing uncontrolled pain. RESULTS: Pain was poorly controlled at baseline, with only 18.1% of patients reporting adequate pain relief (NRS <3.5). All other patients reported uncontrolled pain, with an average NRS of 7.81. At baseline assessment, 47.89% of patients had been in pain for up to 3 months, 32.82% for 3-6 months, and 19.19% for more than 6 months. After baseline assessment, patients were switched to oxycodone CR monotherapy. The starting dose was individualized to each patient and titrated up over a 3- to 4-day period until effective pain management was achieved. Treatment was continued for an average of 37.24 days during the study. Pain control (final mean NRS of 2.85) was attained with an average dose of oxycodone CR 221.84 mg/day. Standard adverse events (including constipations, nausea, and vomiting) were recorded in 39.64% of patients receiving high-dose oxycodone CR monotherapy. Side-effects tended to subside after the initial week of treatment and did not result in any participants leaving the study. CONCLUSION: High-dose oxycodone CR can achieve rapid and effective management of moderate to severe cancer and non-cancer pain with minimum side-effects.