70 Psychosomatic Medicine C LINICAL P SYCHIATRY N EWS • February 2005 Link Between Depression, Mortality Weakened BY HEIDI SPLETE Rose, Ph.D., of Rush University Medical predicted a 21% increase in death from any guishing between clinical depression and Senior Writer Center, Chicago, and her colleagues (Psy- cause after age, race, and gender were ad- poor physical health can be difficult, the in- chosom. Med. 2004;66:823-30). justed for. However, no excess risk of mor- vestigators said. epressive symptoms are not inde- The investigators selected noninstitu- tality was associated with CES-D scores in Patients with scores in the highest quin- pendent predictors of mortality, tionalized adults aged 25 years and older a fully adjusted model that included de- tile on the CES-D had an 85% greater risk Daccording to data from a national who were participating in an ongoing, mographics, education, income, behav- of death from any cause, compared with sample of 3,617 adults. longitudinal study called Americans’ ioral risk factors, and three indicators of participants with the lowest CES-D scores, The findings of previous studies of as- Changing Lives. health status (hypertension, functional im- but no other quintiles showed an increased sociations between depressive symptoms A total of 542 deaths occurred during pairment, and life-threatening conditions). mortality risk, Dr. Everson-Rose and her and mortality have been inconsistent, and 7.5 years of follow-up. Each increase of 1 The physical complaints of patients associates reported. few of these studies have used population- standard unit on the Center for Epidemi- with depression often resemble symptoms Depressive symptoms were not signifi- based samples, said Susan A. Everson- ological Studies Depression scale (CES-D) of other health problems, and distin- cantly associated with mortality risk in a healthy subgroup of 2,833 adults (with 306 deaths) who reported good or excellent BRIEF SUMMARY. See package insert for full prescribing information. co-administering venlafaxine with other drugs affecting the serotonergic neurotransmitter systems, such as triptans, CONTRAINDICATIONS: Hypersensitivity to venlafaxine hydrochloride serotonin reuptake inhibitors, or lithium. Electroconvulsive Therapy (ECT):There are no clinical data establishing the benefit health at baseline. In addition, depressive or to any excipients in the formulation. Concomitant use in patients of ECT combined with Effexor XR treatment. Carcinogenesis, Mutagenesis, Impairment of Fertility—Carcinogenesis: taking monoamine oxidase inhibitors (MAOIs). WARNINGS: Potential There was no increase in tumors in mice and rats given up to 1.7 times the maximum recommended human dose (MRHD) for Interaction with MAOIs—Adverse reactions, some serious, have been reported in patients who recently on a mg/m2 basis. Mutagenesis:Venlafaxine and ODV were not mutagenic in the Ames reverse mutation assay in symptoms were not associated with in- discontinued an MAOI and started on venlafaxine, or who recently discontinued venlafaxine prior to initiation of an Salmonella bacteria or the CHO/HGPRT mammalian cell forward gene mutation assay. Venlafaxine was not clastogenic in MAOI. These reactions included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia several assays. ODV elicited a clastogenic response in the in vivo chromosomal aberration assay in rat bone marrow. creased mortality risk in patients without with features resembling neuroleptic malignant syndrome, seizures, and death. Effexor XR should not be used in Impairment of Fertility: No effects on reproduction or fertility in rats were noted at oral doses of up to 2 times the MRHD combination with an MAOI, or within at least 14 days of discontinuing treatment with an MAOI. At least 7 days on a mg/m2 basis. Pregnancy—Teratogenic Effects—Pregnancy Category C. Reproduction studies in rats given 2.5 functional impairments at baseline. should be allowed after stopping venlafaxine before starting an MAOI. Clinical Worsening and Suicide Risk—Adult times, and rabbits given 4 times the MRHD (mg/m2 basis) revealed no malformations in offspring. However, in rats given 2.5 and pediatric patients with major depressive disorder (MDD) may experience worsening of depression and/or emergence of times the MRHD, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during Although depressive symptoms were suicidal ideation and behavior (suicidality), whether or not taking antidepressants. This risk may persist until significant the first 5 days of lactation when dosing began during pregnancy and continued until weaning. There are no adequate and remission occurs. Although there has long been concern that antidepressants may induce worsening of depression and well-controlled studies in pregnant women; use Effexor XR during pregnancy only if clearly needed. Nonteratogenic Effects. associated with greater physical impair- emergence of suicidality, a causal role has not been established. Closely observe patients treated with antidepressants Neonates exposed to Effexor XR late in the third trimester have developed complications requiring prolonged hospitalization, for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose respiratory support, and tube feeding. Complications can arise immediately upon delivery. Reports include respiratory ment over time after demographics, so- increases or decreases. Consider changing the therapeutic regimen or discontinuing the medication in patients whose distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, MDD is persistently worse or whose emergent suicidality is severe, abrupt in onset, or not part of presenting symptoms. Due hyperreflexia, tremor, jitteriness, irritability, and constant crying. This is consistent with a direct toxic effect of SNRIs or a drug cioeconomic status, and baseline physical to possible comorbidity, when treating patients with other psychiatric and nonpsychiatric disorders, observe the same discontinuation syndrome. In some cases, it is consistent with serotonin syndrome. When treating a pregnant woman with precautions used when treating MDD patients. Anxiety, agitation, panic attacks, insomnia, irritability, hostility Effexor XR during the third trimester, carefully consider the potential risks and benefits of treatment and consider tapering impairment were controlled for, the CES- (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania have been reported in adults and Effexor XR in the third trimester. Labor, Delivery, Nursing—The effect on labor and delivery in humans is unknown. pediatrics treated with antidepressants for MDD and other psychiatric and nonpsychiatric indications. Although a causal link Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions D does not measure clinical depression, between emergence of such symptoms and worsening of depression and/or emergence of suicidal impulses has not been in nursing infants from Effexor XR, a decision should be made whether to discontinue nursing or to discontinue the drug, established, consider changing the therapeutic regimen or discontinuing the medication in patients for whom such taking into account the importance of the drug to the mother. Pediatric Use—Effectiveness in pediatric patients has not which has been studied as a possible link symptoms are severe, abrupt in onset, or not part of presenting symptoms. Alert families and caregivers of patients been established (see WARNINGS-Clinical Worsening and Suicide Risk). No studies have adequately assessed the impact treated with antidepressants for MDD or other psychiatric or nonpsychiatric indications to monitor patients for of Effexor XR on growth, development, and maturation of children and adolescents. Studies suggest Effexor XR may adversely to mortality and cardiovascular health, emergence of agitation, irritability, and other symptoms described above, and emergence of suicidality, and to affect weight and height (see PRECAUTIONS-General, Changes in Height and Changes in Weight). Should the decision be report such symptoms immediately to health care providers. Write prescriptions for Effexor XR for the smallest quantity made to treat a pediatric patient with Effexor XR, regular monitoring of weight and height is recommended during treatment, ■ of capsules consistent with good patient management, to reduce risk of overdose. If it is decided to discontinue treatment, particularly if long term. The safety of Effexor XR for pediatric patients has not been assessed for chronic treatment >6 the investigators noted. medication should be tapered, as rapidly as feasible, but recognizing that abrupt discontinuation can be associated with months. In studies in patients aged 6-17, blood pressure and cholesterol increases considered to be clinically relevant were certain symptoms. Effexor XR is not approved for use in any indications in pediatrics. A major depressive episode may be similar to that observed in adult patients. The precautions for adults apply to pediatric patients. Geriatric Use—No overall the initial presentation of bipolar disorder. It is generally believed treating such an episode with an antidepressant alone may differences in effectiveness or safety were observed between geriatric and younger patients.