- Email: [email protected]
Suicide Among Breast Cancer Patients Who Have Had Reconstructive Surgery: A Population-Based Study
Letters Neuropsychiatry Clin Neurosci 2003; 15:17–26 4. Tenovuo O: Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury: clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:61–67 5. Bennouna M, Greene VB, Defranoux L: Adjuvant galantamine to risperidone improves negative and cognitive symptoms in a patient presenting with schizophrenia-like psychosis after traumatic brain injury. J Clin Psychopharmacol 2005; 25:505–507
Suicide Among Breast Cancer Patients Who Have Had Reconstructive Surgery: A Population-Based Study TO THE EDITOR: Four epidemiological studies have reported an excess of deaths from suicide among women with cosmetic (augmentation) silicone gel-filled breast implants, with a total of 58 deaths from suicide in the four studies (versus 25.2 expected in the general population).1 Other women who have received breast implants are patients with breast cancer who have had reconstruction after mastectomy. To analyze suicide rates in these women, this report used a public-use data file from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program of high-quality, population-based cancer registries.2 For breast cancers diagnosed from 1983 to 1997, breast cancer surgery codes 48, 58, 68, or 78 identified patients with postmastectomy reconstruction as part of the first course of treatment (i.e., planned or administered within the first 4 months after initiation of cancer-directed treatment) in the original nine SEER registries: San Francisco/Oakland CA; Connecticut; Detroit, MI; Hawaii; Iowa; New Mexico; Seattle, WA/Puget Sound WA; Utah; and Atlanta, GA). These registries cover about 10% of the 178
http://psy.psychiatryonline.org
United States population, and these data are often used to estimate U.S. cancer incidence and survival rates. Because patients with reconstruction (by definition) had to survive until reconstruction, a small bias is introduced in analyses of mortality; however, all patients diagnosed in 1983 to 1997 had at least 5 years of survival, and all diagnosed in 1983 to 1992 had at least 10 years of potential follow-up (through the study cut-off date of December 31, 2002). Patients diagnosed in 1998 to 2002 were excluded because of minimal potential follow-up (⬍1 year for some and ⬍5 years for all). Reconstruction is rare in patients with late (metastatic) stage at diagnosis, and declines with age at diagnosis (reaching very low levels after age 70).3 For this study, patients age 15–69 years at diagnosis, with early (in-situ, localized, or regional) stage were included. Second or later primary cancers were excluded. The date of surgery was not available,3 and follow-up was from date (month and year) of breast cancer diagnosis until either death, loss to follow-up, or December 31, 2002. The SEER*Stat 6.1.4 computer program2 was used to calculate risk of death (underlying cause) from suicide and self-inflicted injury (ICD-8 and ICD-9 Codes 950–959 and ICD-10 Codes U02, X60–834, and X87.0). Deaths coded to accidents (ICD-8 and ICD-9 Codes 800–949 and ICD-10 Codes V01–X59 and Y85–Y86) were also analyzed because some may have been suicides. An actuarial method was used, and cumulative death rates (and their standard errors) per 1,000 patients for the specified causes were calculated by time after breast cancer diagnosis. A data file with records for all individual breast cancers was also used for Kaplan-Meier analysis (with SPSS Version 12.0 for Windows) including a log-rank test. Cox proportional-hazards regres-
sion analysis included age at diagnosis (recoded as 15–49, 50–59, and 60–69 years) as a confounder associated with both receipt of reconstruction and risk of death from suicide or accident; 95% confidence intervals (CIs) on hazard ratios (HRs) were based on the normal approximation. The 5-year cumulative death rates from both suicide and accidents in the postmastectomy reconstruction group were similar to those for all other breast cancer patients and also to the subgroup that had mastectomy without reconstruction (Table 1). For 10 years of potential follow-up, including only patients diagnosed in 1983 to 1992, cumulative death rates also differed little. For 10-year follow-up, log-rank tests comparing mastectomy patients with versus those without reconstruction were not statistically significant for suicide (t⳱0.24; p⳱0.625) or accident (t⳱0.65; p⳱0.422). In a Cox proportional-hazards regression model that included age-group, the adjusted HR for suicide was 1.22 (95% CI: 0.59– 2.89) for postmastectomy reconstruction (versus mastectomy without reconstruction). Comparing breast cancer patients with versus without reconstruction is useful, because of the possibility of higher suicide risk (possibly related to depression or other psychological sequelae) of breast cancer patients versus the general population.4 Use of silicone implants for reconstruction was not proscribed in the United States, and use of flap reconstruction was not popularized until the late 1980s; therefore, some of the patients in this study received an implant, but the type was unknown. Other evidence suggests that reconstruction in breast cancer patients may have limited impact on psychosocial outcomes.5 Psychological profiles and risks for suicide may differ between women who obtain implants for Psychosomatics 48:2, March-April 2007
Letters cosmetic augmentation versus postmastectomy reconstruction. This work was supported by Contract NO1-PC-35133 between the U.S. National Cancer Institute and the Connecticut Department of Public Health. Anthony P. Polednak, Ph.D. Connecticut Dept. of Public Health, Hartford, CT
References
1. McLaughlin JK, Wise TN, Lipworth L: Increased risk of suicide among patients with breast implants: do the epidemiologic data support psychiatric consultation? Psychosomatics 2004; 45:277–280 2. National Cancer Institute: Surveillance, Epidemiology, and End Results Program, SEER*Stat 6.1.4. SEER Cancer Incidence Public-Use Data-Base, 1973–2002, produced 4/28/2005; Bethesda MD, CDROM 3. Morrow M, Scott SK, Menck HR, et al: Factors influencing breast reconstruction mastectomy: a National Cancer Database Study. J Am Coll Surg 2001; 192:1–8 4. Hjerl K, Andersen EW, Keiding N, et al: Increased incidence of affective disorders, anxiety disorders, and non-natural mortality in women after breast cancer diagnosis: a nationwide cohort study in Denmark. Acta Psychiatr Scand 2002; 105:258–264 5. Rowland JH, Desmond KA, Meyerowitz BE, et al: Role of breast reconstructive
TABLE 1.
surgery in physical and emotional outcomes among breast cancer survivors. J Natl Cancer Inst 2000; 92:1422–1429
An Acute Attack of Porphyria in a Patient Taking Duloxetine TO THE EDITOR: Variegate porphyria shares with other acute porphyrias the symptom triad of red rash, abdominal pain, and neuropsychiatric disturbances.1 It also shares exhaustive lists of “safe” and “unsafe” medications.2 To our knowledge, this is the first report of a porphyria patient who suffered a severe adverse reaction typical of an acute porphyria exacerbation shortly after exposure to duloxetine. A white woman in her sixth decade, with a history of back pain and fibromyalgia, also experienced episodes of red rash with severe abdominal pain. Depression and anxiety followed. After several years, variegate porphyria was established by identifying porphyrins in a 24-hour urine sample, with coproporphyrin quantities greater than aminolevulinic acid and porphobilinogen, with coproporphyrin present in fecal samples, and with these
same porphyrins present in serum assays. After tolerating a seemingly unsuccessful trial of extended-release venlafaxine for treatment of depression and anxiety and for pain prophylaxis, she was tapered from venlafaxine and prescribed another serotonin- and norepinephrine-reuptake inhibitor antidepressant, duloxetine. No other medication changes were made. After 4 days of duloxetine therapy, she experienced her “worst attack in years,” with a painful and ulcerating red rash, severe abdominal pain with constipation and vomiting, paresthesias, and worsening depression and anxiety, along with hallucinations, paranoia, and suicidality. Delirium ensued. These symptoms rapidly abated with cessation of duloxetine, opioid analgesia, and Panhematin威 therapy. When heme-biosynthesis is disordered by pathway enzyme deficiencies, porphyrins or their precursors can accumulate and result in dangerous toxicity.3 Since heme is an essential component in cytochrome P450 enzymes, induction of this system in the liver increases heme-synthesis, thus exaggerating the existing heme genetic
Cumulative Numbers of Deaths and Cumulative Death Rates (per 1,000) From Suicide and Accidents Among Breast Cancer Patients Diagnosed in 1983–1997 at Age 15–69 Years in Areas Covered by the Surveillance, Epidemiology, and End Results (SEER) Program Suicide
Breast Reconstruction Yes No/All patients No/With mastectomyb Yes No/All patients No/With mastectomyb
Total
Alive at Starta
Number
Accident Rate (95% CI)
Cumulative Deaths and Cumulative Death Rate at 5 Years After Diagnosis 7,154 6,579 4 0.6 (0.0–1.2) 132,733 117,530 61 0.5 (0.3–0.6) (75,102) (64,689) (42) 0.6 (0.4–0.8) Cumulative Deaths and Cumulative Death Rate at 10 Years After Diagnosis 7,154 2,991c 6 1.0 (0.2–1.8) 132,733 68,285c 80 0.7 (0.5–0.8) (75,102) (41,969)c (51) 0.7 (0.5–0.9)
Number
Rate (95% CI)
6 106 (69)
0.8 (0.1–1.5) 0.8 (0.6–1.0) 0.9 (0.7–1.1)
9 201 (128)
1.6 (0.5–2.7) 1.7 (1.5–1.9) 1.8 (1.5–2.2)
CI: confidence interval (95%) estimated as twice the standard error of the cumulative death rate (sum of death rates during each 1-year interval), by use of an actuarial method.2 a Number of patients alive at the start of the time interval (in years) after diagnosis. b A subgroup of all patients without reconstruction. c Only patients diagnosed in 1983–1992 had 10 years of potential follow-up after diagnosis.
Psychosomatics 48:2, March-April 2007
179
Suicide Among Breast Cancer Patients Who Have Had Reconstructive Surgery: A Population-Based Study TO THE EDITOR: Four epidemiological studies have reported an excess of deaths from suicide among women with cosmetic (augmentation) silicone gel-filled breast implants, with a total of 58 deaths from suicide in the four studies (versus 25.2 expected in the general population).1 Other women who have received breast implants are patients with breast cancer who have had reconstruction after mastectomy. To analyze suicide rates in these women, this report used a public-use data file from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program of high-quality, population-based cancer registries.2 For breast cancers diagnosed from 1983 to 1997, breast cancer surgery codes 48, 58, 68, or 78 identified patients with postmastectomy reconstruction as part of the first course of treatment (i.e., planned or administered within the first 4 months after initiation of cancer-directed treatment) in the original nine SEER registries: San Francisco/Oakland CA; Connecticut; Detroit, MI; Hawaii; Iowa; New Mexico; Seattle, WA/Puget Sound WA; Utah; and Atlanta, GA). These registries cover about 10% of the 178
http://psy.psychiatryonline.org
United States population, and these data are often used to estimate U.S. cancer incidence and survival rates. Because patients with reconstruction (by definition) had to survive until reconstruction, a small bias is introduced in analyses of mortality; however, all patients diagnosed in 1983 to 1997 had at least 5 years of survival, and all diagnosed in 1983 to 1992 had at least 10 years of potential follow-up (through the study cut-off date of December 31, 2002). Patients diagnosed in 1998 to 2002 were excluded because of minimal potential follow-up (⬍1 year for some and ⬍5 years for all). Reconstruction is rare in patients with late (metastatic) stage at diagnosis, and declines with age at diagnosis (reaching very low levels after age 70).3 For this study, patients age 15–69 years at diagnosis, with early (in-situ, localized, or regional) stage were included. Second or later primary cancers were excluded. The date of surgery was not available,3 and follow-up was from date (month and year) of breast cancer diagnosis until either death, loss to follow-up, or December 31, 2002. The SEER*Stat 6.1.4 computer program2 was used to calculate risk of death (underlying cause) from suicide and self-inflicted injury (ICD-8 and ICD-9 Codes 950–959 and ICD-10 Codes U02, X60–834, and X87.0). Deaths coded to accidents (ICD-8 and ICD-9 Codes 800–949 and ICD-10 Codes V01–X59 and Y85–Y86) were also analyzed because some may have been suicides. An actuarial method was used, and cumulative death rates (and their standard errors) per 1,000 patients for the specified causes were calculated by time after breast cancer diagnosis. A data file with records for all individual breast cancers was also used for Kaplan-Meier analysis (with SPSS Version 12.0 for Windows) including a log-rank test. Cox proportional-hazards regres-
sion analysis included age at diagnosis (recoded as 15–49, 50–59, and 60–69 years) as a confounder associated with both receipt of reconstruction and risk of death from suicide or accident; 95% confidence intervals (CIs) on hazard ratios (HRs) were based on the normal approximation. The 5-year cumulative death rates from both suicide and accidents in the postmastectomy reconstruction group were similar to those for all other breast cancer patients and also to the subgroup that had mastectomy without reconstruction (Table 1). For 10 years of potential follow-up, including only patients diagnosed in 1983 to 1992, cumulative death rates also differed little. For 10-year follow-up, log-rank tests comparing mastectomy patients with versus those without reconstruction were not statistically significant for suicide (t⳱0.24; p⳱0.625) or accident (t⳱0.65; p⳱0.422). In a Cox proportional-hazards regression model that included age-group, the adjusted HR for suicide was 1.22 (95% CI: 0.59– 2.89) for postmastectomy reconstruction (versus mastectomy without reconstruction). Comparing breast cancer patients with versus without reconstruction is useful, because of the possibility of higher suicide risk (possibly related to depression or other psychological sequelae) of breast cancer patients versus the general population.4 Use of silicone implants for reconstruction was not proscribed in the United States, and use of flap reconstruction was not popularized until the late 1980s; therefore, some of the patients in this study received an implant, but the type was unknown. Other evidence suggests that reconstruction in breast cancer patients may have limited impact on psychosocial outcomes.5 Psychological profiles and risks for suicide may differ between women who obtain implants for Psychosomatics 48:2, March-April 2007
Letters cosmetic augmentation versus postmastectomy reconstruction. This work was supported by Contract NO1-PC-35133 between the U.S. National Cancer Institute and the Connecticut Department of Public Health. Anthony P. Polednak, Ph.D. Connecticut Dept. of Public Health, Hartford, CT
References
1. McLaughlin JK, Wise TN, Lipworth L: Increased risk of suicide among patients with breast implants: do the epidemiologic data support psychiatric consultation? Psychosomatics 2004; 45:277–280 2. National Cancer Institute: Surveillance, Epidemiology, and End Results Program, SEER*Stat 6.1.4. SEER Cancer Incidence Public-Use Data-Base, 1973–2002, produced 4/28/2005; Bethesda MD, CDROM 3. Morrow M, Scott SK, Menck HR, et al: Factors influencing breast reconstruction mastectomy: a National Cancer Database Study. J Am Coll Surg 2001; 192:1–8 4. Hjerl K, Andersen EW, Keiding N, et al: Increased incidence of affective disorders, anxiety disorders, and non-natural mortality in women after breast cancer diagnosis: a nationwide cohort study in Denmark. Acta Psychiatr Scand 2002; 105:258–264 5. Rowland JH, Desmond KA, Meyerowitz BE, et al: Role of breast reconstructive
TABLE 1.
surgery in physical and emotional outcomes among breast cancer survivors. J Natl Cancer Inst 2000; 92:1422–1429
An Acute Attack of Porphyria in a Patient Taking Duloxetine TO THE EDITOR: Variegate porphyria shares with other acute porphyrias the symptom triad of red rash, abdominal pain, and neuropsychiatric disturbances.1 It also shares exhaustive lists of “safe” and “unsafe” medications.2 To our knowledge, this is the first report of a porphyria patient who suffered a severe adverse reaction typical of an acute porphyria exacerbation shortly after exposure to duloxetine. A white woman in her sixth decade, with a history of back pain and fibromyalgia, also experienced episodes of red rash with severe abdominal pain. Depression and anxiety followed. After several years, variegate porphyria was established by identifying porphyrins in a 24-hour urine sample, with coproporphyrin quantities greater than aminolevulinic acid and porphobilinogen, with coproporphyrin present in fecal samples, and with these
same porphyrins present in serum assays. After tolerating a seemingly unsuccessful trial of extended-release venlafaxine for treatment of depression and anxiety and for pain prophylaxis, she was tapered from venlafaxine and prescribed another serotonin- and norepinephrine-reuptake inhibitor antidepressant, duloxetine. No other medication changes were made. After 4 days of duloxetine therapy, she experienced her “worst attack in years,” with a painful and ulcerating red rash, severe abdominal pain with constipation and vomiting, paresthesias, and worsening depression and anxiety, along with hallucinations, paranoia, and suicidality. Delirium ensued. These symptoms rapidly abated with cessation of duloxetine, opioid analgesia, and Panhematin威 therapy. When heme-biosynthesis is disordered by pathway enzyme deficiencies, porphyrins or their precursors can accumulate and result in dangerous toxicity.3 Since heme is an essential component in cytochrome P450 enzymes, induction of this system in the liver increases heme-synthesis, thus exaggerating the existing heme genetic
Cumulative Numbers of Deaths and Cumulative Death Rates (per 1,000) From Suicide and Accidents Among Breast Cancer Patients Diagnosed in 1983–1997 at Age 15–69 Years in Areas Covered by the Surveillance, Epidemiology, and End Results (SEER) Program Suicide
Breast Reconstruction Yes No/All patients No/With mastectomyb Yes No/All patients No/With mastectomyb
Total
Alive at Starta
Number
Accident Rate (95% CI)
Cumulative Deaths and Cumulative Death Rate at 5 Years After Diagnosis 7,154 6,579 4 0.6 (0.0–1.2) 132,733 117,530 61 0.5 (0.3–0.6) (75,102) (64,689) (42) 0.6 (0.4–0.8) Cumulative Deaths and Cumulative Death Rate at 10 Years After Diagnosis 7,154 2,991c 6 1.0 (0.2–1.8) 132,733 68,285c 80 0.7 (0.5–0.8) (75,102) (41,969)c (51) 0.7 (0.5–0.9)
Number
Rate (95% CI)
6 106 (69)
0.8 (0.1–1.5) 0.8 (0.6–1.0) 0.9 (0.7–1.1)
9 201 (128)
1.6 (0.5–2.7) 1.7 (1.5–1.9) 1.8 (1.5–2.2)
CI: confidence interval (95%) estimated as twice the standard error of the cumulative death rate (sum of death rates during each 1-year interval), by use of an actuarial method.2 a Number of patients alive at the start of the time interval (in years) after diagnosis. b A subgroup of all patients without reconstruction. c Only patients diagnosed in 1983–1992 had 10 years of potential follow-up after diagnosis.
Psychosomatics 48:2, March-April 2007
179