Because it is the third leading cause of death in children over 15, here is a review article updated by: David Taylor, M.D., Department of Psychiatry, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network.

Suicide is the act of deliberately taking one's own life. Suicidal behavior is any deliberate action with potentially life-threatening consequences, such as taking a drug overdose or deliberately crashing a car.

Suicidal behaviors can accompany many emotional disturbances, including depression, bipolar disorder, and schizophrenia. More than 90% of all suicides are related to a mood disorder or other psychiatric illness. Suicidal behaviors often occur as a response to a situation that the person views as overwhelming, such as social isolation, death of a loved one, emotional trauma, serious physical illness, growing old, unemployment or financial problems, guilt feelings, and alcohol or other drug dependence. In the U.S., suicide accounts for about 1% of all deaths each year. The highest rate is among the elderly, but there has been a steady increase in the rate among adolescents. Suicide is now the third leading cause of death for those 15 to 19 years old, after accidents and homicide.
Suicide attempts that do not result in death far outnumber completed suicides. Many unsuccessful suicide attempts are carried out in a manner that makes rescue possible. They often represent a desperate cry for help.

The method of suicide varies from relatively nonviolent methods (such as poisoning or overdose) to violent methods (such as shooting oneself). Males are more likely to choose violent methods, which probably accounts for the fact that suicide attempts by males are more likely to be completed.
Suicide attempts should always be taken seriously and mental health care should be sought immediately. Dismissing them as "attention seeking" can have devastating consequences.

Relatives of people who seriously attempt or complete suicide often blame themselves or become extremely angry, seeing the attempt or act as selfish. However, when people are suicidal, they often mistakenly believe that they are doing their friends and relatives a favor by taking themselves out of the world and these irrational beliefs often drive their behavior.

Early signs:
· depression
· statements or expressions of guilt feelings
· tension or anxiety
· nervousness
· impulsiveness

Critical signs:
· sudden change in behavior (especially calmness after a period of anxiety)
· giving away belongings, attempts to "get one's affairs in order"
· direct or indirect threats to commit suicide
· direct attempts to commit suicide

Treatment

Emergency measures may be necessary after a person has attempted suicide. First aid, CPR or mouth-to-mouth resuscitation may be required.
Hospitalization is often needed, both to treat the recent actions and to prevent future attempts. Psychiatric intervention is one of the most important aspects of treatment.

Expectations (prognosis)

All suicide threats and attempts should be taken seriously. About one-third of people who attempt suicide will repeat the attempt within one year, and about 10% of those who threaten or attempt suicide eventually do kill themselves.

Complications

Complications vary depending on the type of suicide attempt.
Call your health care provider.
A person who threatens or attempts suicide MUST be evaluated by a mental health professional promptly. NEVER IGNORE A SUICIDE THREAT OR ATTEMPT!

Prevention

Many people who attempt suicide talk about it before making the attempt. Often, the ability to talk to a sympathetic, nonjudgmental listener is enough to prevent the person from attempting suicide. For this reason suicide prevention centers have telephone "hotline" services. Again, do not ignore a suicide threat or attempted suicide.

As with any other type of emergency, it is best to immediately call the local emergency number (such as 911). Do not leave the person alone even after phone contact with an appropriate professional has been made.

In a large meta-analysis that included 361 controlled studies that (1) evaluated at least one treatment for alcohol use disorders, (2) compared it with an alternative condition (such as a control

group, a placebo, a brief intervention or an alternative treatment), (3) used a procedure designed to create equivalent groups before treatment and (4) reported at least one outcome measure of drinking or alcohol-related consequences.

Least supported were methods designed to educate, confront, shock or foster insight regarding the nature and causes of alcoholism.

Fluoxetine (PROZAC) After Weight Restoration

in Anorexia

JAMA 2006;295:2577.

.Antidepressant medications are often prescribed to patients

with anorexia nervosa during the acute treatment phase, despite

a lack of evidence of the efficacy of these drugs for this disorder.

Walsh and colleagues report results of a randomized placebo-controlled

trial that assessed whether fluoxetine promotes recovery and prolongs

the time to relapse after weight restoration in patients with anorexia.

The authors found no benefit of fluoxetine relative to placebo for

maintenance of minimum body mass index or time to relapse during

the 12-month study.

In an editorial, Crow discusses treatment of anorexia nervosa, adherence

with treatment, and relapse prevention.

JAMA -- This Week in JAMA, June 14, 2006, 295 (22) 2577

Use of Antipsychotics by the Young Rose Fivefold

By BENEDICT CAREY

New York Times

June 6, 2006

The use of potent antipsychotic drugs to treat children and adolescents for problems like aggression and mood swings increased more than fivefold from 1993 to 2002, researchers reported yesterday.

The researchers, who analyzed data from a national survey of doctors' office visits, found that antipsychotic medications were prescribed to 1,438 per 100,000 children and adolescents in 2002, up from 275 per 100,000 in the two-year period from 1993 to 1995.

The findings augment earlier studies that have documented a sharp rise over the last decade in the prescription of psychiatric drugs for children, including antipsychotics, stimulants like Ritalin and antidepressants, whose sales have slipped only recently. But the new study is the most comprehensive to examine the increase in prescriptions for antipsychotics.

The explosion in the use of drugs, some experts said, can be traced in part to the growing number of children and adolescents whose problems are given psychiatric labels once reserved for adults and to doctors' increasing comfort with a newer generation of drugs for psychosis. Shrinking access to long-term psychotherapy and hospital care may also play a role, the experts said.

The findings, published June 5, 2006 in Archives of General Psychiatry, are likely to inflame a continuing debate about the risks of using psychiatric medication in children. In recent years, antidepressants have been linked to an increase in suicidal thinking or behavior in some minors, and reports have suggested that stimulant drugs like Ritalin may exacerbate underlying heart problems.

Antipsychotic drugs also carry risks: Researchers have found that many of the drugs can cause rapid weight gain and blood lipid changes that increase the risk of diabetes. None of the most commonly prescribed antipsychotics is approved for use in children, although doctors can prescribe any medication that has been approved for use. Experts said that little was known about the use of antipsychotics in minors: only a handful of small studies have been done in children and adolescents.

"We are using these medications and don't know how they work, if they work, or at what cost," said Dr. John March, a professor of child and adolescent psychiatry at Duke University. "It amounts to a huge experiment with the lives of American kids, and what it tells us is that we've got to do something other than we're doing now" to assess the drugs' overall impact.

But many child psychiatrists say that antipsychotic medication is the best therapy available for children in urgent need of help who do not respond well to other treatments. Without them, they say, many unpredictable, emotionally unstable children would end up institutionalized.

Dr. Mark Olfson, a professor of clinical psychiatry at Columbia University and the lead author of the study, financed in part by the National Institute of Mental Health, said the popularity of antipsychotic drugs might result in part from "the fact that psychiatrists have few other pharmacological options in certain patients." The study, which looked at visits to pediatricians and other doctors, found that psychiatrists were the most likely to prescribe antipsychotic drugs. In light of how little these drugs have been studied in children, Dr. Olfson said, "to me the most striking thing was that nearly one in five psychiatric visits for young people included a prescription for antipsychotics."

The Columbia investigators analyzed data from the National Center for Health Statistics survey of office visits, which focuses on doctors in private or group practices. They calculated the number of visits in which an antipsychotic drug was prescribed to people under the age of 21 and collected information on patients' medical histories. The total number of visits that resulted in prescriptions for the drugs increased to 1,224,000 in 2002 from 201,000 1993 to 1995.

The researchers attributed some of the increase to the availability of a new class of drugs for psychosis, called atypical antipsychotics, that were introduced in the early and mid-1990's. The newer drugs, heavily marketed by their makers, were attractive in part because they appeared less likely than older types of antipsychotics to cause side effects like tardive dyskinesia, a neurological movement disorder similar to Parkinson's disease.

From 2000 to 2002, the new study found, more than 90 percent of the prescriptions analyzed were for the newer medications, and most of the patients were boys, predominantly Caucasian children, who were significantly more likely to see psychiatrists than other ethnic groups. Some experts also pointed to an increase in the diagnosis of bipolar disorder in children as a contributing factor. In recent years, psychiatrists have begun to diagnose the disorder in extremely agitated, often aggressive children with mood swings — short surges of grandiosity or irritation that alternate with periods of despair. These symptoms in children are thought to be related to the classic euphoria and depressions of adult bipolar disorder.

At the same time, several of the atypical antipsychotics, including Risperdal from Janssen and Zyprexa from Eli Lilly, won approval for the treatment of mania in adults. Some psychiatrists now routinely prescribe atypical antipsychotics "off label" for young people thought to have bipolar disorder, and researchers have begun to study the drugs in children as young as preschool age.

In the new study, about a third of the children who received antipsychotics had behavior disorders, which included attention deficit problems; a third had psychotic symptoms or developmental problems; and another third were suffering from mood disorders. Over all, more than 40 percent of the children were also taking at least one other psychiatric medication.

"We feel the medications are effective in children with bipolar and have some data to show that," said Dr. Melissa DelBello, an associate professor of psychiatry at the University of Cincinnati, who has done several studies of the drugs. Dr. DelBello said that the field "desperately needs more research" to clarify the effects of the antipsychotic drugs but that many children struggling with bipolar disorder got more symptom relief on these drugs than on others, allowing psychiatrists to cut down on the overall number of medications a child is taking. Lisa Pedersen of Dallas, the mother of a 17-year-old boy being treated for bipolar disorder, said he was unpredictable, hostile and suicidal before psychiatrists found an effective cocktail of drugs, which includes a daily dose of antipsychotic medication.

"Believe me, I would never choose having him on these meds," Ms. Pedersen said in a telephone interview. "It's not fun watching a child deal with the side effects. But finding the right combination of medicine has made his life worth living."

Yet this process is one of trial and error for many children. Ms. Pedersen said her son had responded badly to the first two antipsychotic drugs he received. And some experts think the way that psychiatric drugs are prescribed is obscuring any understanding of underlying disorders and the optimal treatments.

"If you're going to put children on three or four different drugs, now you've got a potpourri of target symptoms and side effects," said Dr. Julie Magno Zito, an associate professor of pharmacy and medicine at the University of Maryland. Dr. Zito added, "How do you even know who the kid is anymore?"

* * *

Rye Hospital Center Doctors Page

Medication Dosing and Blood Levels

Rye Hospital Center is acutely aware of the changes in our knowledge and the importance of keeping up to date with the latest changes in science-based 21st Century medicine. What matters is not so much how much is ingested but rather, how much of the medication enters the blood stream.

There are three primary factors that influence the amount of drug that finds its way into the blood stream. First is the rate of liver metabolism. Bipolar medications are absorbed through the walls of the stomach and intestines and go directly to the liver, although some are able to be changed directly in the intestines or kidney. In the liver, the drug molecules are acted upon by liver enzymes that begin a process generally referred to as biotransformation. Liver enzymes chemically alter the medication in ways that allow the drug to be more readily excreted from the body. The liver's function is to detoxify the body. Thus, in this so-called first pass effect through the liver, a good deal of the drug is transformed and then rapidly excreted. However, some of the medication initially escapes this process, makes its way through the liver and into circulation and thus is allowed to begin accumulating in the blood stream. How rapidly the liver metabolizes drugs depends on a number of factors. This resulting blood level is what matters when it comes to reducing symptoms. (Note: two mood stabilizers are not metabolized in the liver and are directly excreted by the kidneys: lithium and Neurontin. However, Neurontin is not FDA-approved for bipolar disorder).

The Art of Modern Medicine: Our genes play a significant role in this process. A small percentage of people are known as rapid metabolizers. They take certain drugs and then eliminate them very quickly. The result is that even though they may be taking what seems like an adequate dose of the medication, little actually gets into the blood stream. Once it is discovered that someone is a rapid metabolizer, then usually they are prescribed very high doses of medications and eventually enough gets into the blood stream to be effective. Again, this has nothing to do with how severely ill they are …it's just a matter of the liver's metabolic rate. Conversely, some people are slow-metabolizers. This also small percentage of people, have fewer than average liver enzymes to breakdown these drugs. The effect is that they can take a very small dose of a medication, and on its trip through the liver, only small amounts are transformed and excreted. The result is often very high blood levels of the medication and severe side effects or toxicity. The ultimate solution for slow-metabolizers thus is to use very small doses. Sometimes when a person is first treated they will experience serious side effects and this may be due to slow-metabolizing. It is often hard to know ahead of time if this will happen with any one given individual. Thus if your patient (or their birth parents) has had an experience of encountering very intense side effects with other medications in the past, one may anticipate that they are slow-metabolizers, and thus initial dosing is done gradually.

A second factor determining blood levels of medications is the functioning of the kidney. Sometimes genetic factors play a role here too, but more often problems can occur due to kidney disease. Thus, for some bipolar medications, pre-treatment or baseline laboratory studies will include an assessment of kidney functioning (this is especially important for patients being treated with lithium).

Finally, and increasingly, a number of drugs (even some foods) can adversely affect liver metabolism and thus alter blood levels. Here is where drug-drug interactions can cause significant problems (see article below this one). This applies to many prescription drugs, over-the-counter drugs, herbal and dietary supplement products and recreational drugs. The use of prescription drugs must be carefully monitored by the treating physician. In addition, even modest amounts of alcohol can have significant affects on the liver. For example, St. John's Wort, a popular herbal product for the treatment of depression, is well known for causing some very significant changes in liver metabolism.

* * *

Cardiac Effects of New Psychiatric Medications

With increasing concern over potential toxic effects of new drugs on the heart, Rye Hospital has begun to measure special aspects of electrocardiograms, which could signify the possibility of a dangerous event occurring.

The case in point is the measurement of what is called the "QTc" interval--that electrical part of the heartbeat which may be prolonged either by certain drugs or by combinations of drugs that could produce fatal arrhythmias.

All patients are routinely given a "baseline" cardiogram. Those who require the use of the newer drugs or combinations of drugs that can be additive in their cardiac conduction effects, and prolong the corrected QT interval (QTc), have repeated studies to determine whether they should need a change.

Indeed, because even some antibiotics and foods like grapefruit and/or its juice can cause such critical, additional problems, we constantly endeavor to make our doctors aware of the latest findings by researchers.

* * *

From the American Psychiatric Association

Practice Guideline for the Treatment of Patients With Bipolar Disorder (Revision)

PART A:
Treatment Recommendations for Patients With Bipolar Disorder

III. SPECIAL CLINICAL FEATURES INFLUENCING THE TREATMENT PLAN

A. Psychiatric Features

1. Psychosis
Psychotic symptoms (e.g., delusions, hallucinations) are commonly seen during episodes of either mania or depression but are more common in the former, appearing in over one-half of manic episodes (41). Mood-congruent features during a manic episode probably are not predictive of a poorer outcome, although early onset (before age 21) of psychotic mania may predict a more severe disorder (42). Mood-incongruent features have been identified in some (43) but not all (44) studies to be a predictor of a shorter time in remission. The presence of psychotic features during a manic episode may not require an antipsychotic medication, although most clinicians prescribe them in addition to a maintenance agent (45).

2. Catatonia
Catatonic features may develop in up to one-third of patients during a manic episode (46). The most commonly observed symptoms of catatonia in mania are motor excitement, mutism, and stereotypic movements. Because catatonic symptoms are seen in other psychiatric and neurological disorders, a careful assessment is indicated for an accurate diagnosis. In addition, patients who exhibit catatonic stupor may go on to show more typical signs and symptoms of mania during the same episode of illness (47). The presence of catatonic features during the course of a manic episode is associated with greater episode severity, mixed states, and somewhat poorer short-term outcomes (46). In treating catatonia, neuroleptics have generally exhibited poor efficacy (48). In contrast, prospective studies have demonstrated the efficacy of lorazepam in the treatment of catatonic syndromes, including those associated with mania (49-52). Since ECT is probably the most effective treatment for catatonic syndromes regardless of etiology, ECT should be considered if benzodiazepines do not result in symptom resolution (48).

3. Risk of suicide, homicide, and violence
Like those suffering from major depression, patients with bipolar disorder are at high risk for suicide (53,54). The frequency of suicide attempts appears similar for the bipolar I and bipolar II subtypes (55,56). Individuals with bipolar disorder repeatedly have been shown to have greater overall mortality than the general population (41). Although much of this risk reflects the higher rate of suicide, cardiovascular and pulmonary mortality among patients with untreated bipolar disorder is also high (41,57).

Known general risk factors for suicide also apply to patients with bipolar disorder. These include a history of suicide attempts, suicidal ideation, comorbid substance abuse, comorbid personality disorders (58), agitation, pervasive insomnia, impulsiveness (59), and family history of suicide. Among the phases of bipolar disorder, depression is associated with the highest suicide risk, followed by mixed states and presence of psychotic symptoms, with episodes of mania being least associated with suicide (8,56). Suicidal ideation during mixed states has been correlated with the severity of depressive symptoms (10). In general, a detailed evaluation of the individual patient is necessary to assess suicidal risk (Table 1). Judgment of suicidal risk is inherently imperfect; therefore, risks and benefits of intervention should be carefully weighed and documented.

Long-term treatment with lithium has been associated with reduction of suicide risk (56,60). Whether this reflects an anti-impulsivity factor beyond lithium's mood-stabilizing effect is not yet clear. Lithium may also diminish the greater mortality risk observed among bipolar disorder patients from causes other than suicide (61). It is unknown whether prolonged survival is also seen with the anticonvulsant maintenance agents.

Clinical experience attests to the presence of violent behavior in some patients with bipolar disorder, and violence may be an indication for hospitalization (41). Comorbid substance abuse and psychosis may contribute to the threat of criminal violence or aggression (62-64).

4. Substance use disorders
Bipolar disorder with a comorbid substance use disorder is a very common presentation, with bipolar disorder patients of both sexes showing much higher rates of substance use than the general population (65). For example, the Epidemiologic Catchment Area study found rates of alcohol abuse or dependence in 46% of patients with bipolar disorder compared with 13% for the general population. Comparable drug abuse and dependence figures are 41% and 6%, respectively (66,67). Substance abuse may obscure or exacerbate endogenous mood swings. Conversely, comorbid substance use disorder may be overlooked in patients with bipolar disorder (68,69). Substance abuse may also precipitate mood episodes or be used by patients to ameliorate the symptoms of such episodes. Comorbid substance use is typically associated with fewer and slower remissions, greater rates of suicide and suicide attempts, and poorer outcome (70-73).

Treatment for substance abuse and bipolar disorder should proceed concurrently when possible. It is also helpful to obtain consultation from an addiction expert, such as an addiction psychiatrist, or to arrange for concomitant treatment of the bipolar disorder and the substance use disorder in a dual-diagnosis program.

Alcohol abuse and its effects may affect bipolar disorder pharmacotherapy. For instance, alcohol-related dehy-dration may raise lithium levels to toxicity. Hepatic dysfunction from chronic alcohol abuse or from hepatitis associated with intravenous substance use may alter plasma levels of valproate and carbamazepine (74). If the hepatic dysfunction is severe, the use of these hepatically metabolized medications may be problematic. In these cases, coordination with the patient's primary care physician or gastroenterologist is recommended (75).

5. Comorbid psychiatric conditions
Patients with comorbid personality disorders pose complicated diagnostic pictures. They are clearly at greater risk for experiencing intrapsychic and psychosocial stress that can precipitate or exacerbate mood episodes. Patients with comorbid personality disorders generally have greater symptom burden, lower recovery rates from episodes, and greater functional impairment (76). In addition, these patients may have particular difficulty adhering to long-term treatment regimens (77).

Relative to the general population, individuals with bipolar disorder are at greater risk for comorbid anxiety disorders, especially panic disorder and obsessive-compulsive disorder. Comorbid anxiety disorders may predict a longer time to recovery of mood episodes (78). Treatment for the bipolar disorder and the comorbid anxiety disorder should proceed concurrently.

The presence of comorbid attention deficit hyperactivity disorder (ADHD) in adults and children with bipolar disorder may make it difficult to monitor changes in mood states. Of note, adults with bipolar disorder and comorbid ADHD are likely to have experienced a much earlier age at onset of their mood disorder relative to those without comorbid ADHD (79).

B. Demographic and Psychosocial Factors

1. Gender
A number of issues related to gender must be considered when treating patients with bipolar disorder. Hypothyroidism is more common in women, and women may be more susceptible to the antithyroid effects of lithium (80). Additionally, rapid cycling is more common in women (81,82). Treatment with antipsychotics and, to a lesser extent, SSRIs may elevate serum levels of prolactin and result in galactorrhea, sexual dysfunction, menstrual disorders, and impaired fertility (83,84).

2. Pregnancy
Because many medications used to treat bipolar disorder are associated with a higher risk of birth defects, the psychiatrist should encourage effective contraceptive practices for all female patients of childbearing age who are receiving pharmacological treatment (85,86). Since carbamazepine, oxcarbazepine, and topiramate increase the metabolism of oral contraceptives, women taking these medications should not rely on oral contraceptives for birth control (87-89). This effect does not occur with other medications used to treat bipolar disorder.

Multiple clinical issues arise in relationship to pregnancy in bipolar disorder patients. In order to permit discussion of the risks and benefits of therapeutic options, a pregnancy should be planned in consultation with the psychiatrist whenever possible. Because of the higher genetic risk for bipolar disorder (90-92), patients with bipolar disorder who are considering having children may also benefit from genetic counseling (22).

a) Continuing/discontinuing medications.    Around the time of pregnancy, the risks and benefits of continuing versus discontinuing treatment require the most thoughtful judgment and discussion among the patient, the psychiatrist, the obstetrician, and the father. Specific options include continuing medication throughout pregnancy, discontinuing medications at the beginning of pregnancy or before conception, and discontinuing the medication only for the first trimester.

In clinical decision making, the potential teratogenic risks of psychotropic medications must be balanced against the risk of no prophylactic treatment, with the attendant risks of illness (93). Although the course of bipolar disorder during pregnancy is still unclear, some evidence suggests that pregnancy does not alter the rate of mood episodes compared with other times (94). However, in patients who have been stable on a regimen of lithium, the rate of recurrent mood episodes is clearly increased by lithium discontinuation, particularly when discontinuation is abrupt (94). Should the decision be made to discontinue medication, the woman should be advised about the potentially greater risk of mood episode recurrence with rapid discontinuation of lithium (and possibly other maintenance agents) compared with a slower taper over many weeks (95).

Although direct evidence of a negative effect of untreated psychiatric disorders on fetal development is lacking, antenatal stress, depression, and anxiety are linked with a variety of abnormalities in newborns (96-101). Additionally, during a manic episode, women are at risk of increasing their consumption of alcohol and other drugs, thus conferring additional dangers to the fetus.

b) Prenatal exposure to medications.    First-trimester exposure to lithium, valproate, or carbamazepine is associated with a greater risk of birth defects. With lithium exposure the absolute risk for Ebstein's anomaly, a cardiovascular defect, is 1-2 per 1,000. This is approximately 10-20 times greater than the risk in the general population (102). Exposure to carbamazepine and valproate during the first trimester is associated with neural tube defects at rates of up to 1% and 3%-5%, respectively (85). Both carbamazepine and valproate exposure have also been associated with craniofacial abnormalities (103,104). Other congenital defects that have been observed with valproate include limb malformations and cardiac defects (104). Little is known about the potential teratogenicity of lamotrigine, gabapentin, or other newer anticonvulsants.

No teratogenic effects have been demonstrated with tricyclic antidepressants. Near term, however, their use has been associated with side effects in the neonate (105). The SSRIs seem to be relatively benign in their risks to exposed fetuses (106), with safety data being strongest for fluoxetine and citalopram. Although data with bupropion, mirtazapine, nefazodone, trazodone, and venlafaxine are limited (105), none of the newer antidepressants has been shown to be teratogenic (106,107). Nonetheless, caution must be exercised if they are prescribed to treat bipolar depression in pregnant women (93).

Antipsychotic agents may be needed to treat psychotic features of bipolar disorder during pregnancy, but they may also represent an alternative to lithium for treating symptoms of mania (105). High-potency antipsychotic medications are preferred during pregnancy, since they are less likely to have associated anticholinergic, antihistaminergic, or hypotensive effects. In addition, there is no evidence of teratogenicity with exposure to haloperidol, perphenazine, thiothixene, or trifluoperazine (105). When high-potency antipsychotic medications are used near term, neonates may show extrapyramidal side effects, but these are generally short-lived (108). To limit the duration of such effects, however, long-acting depot preparations of antipsychotic medications are not recommended during pregnancy (105). For newer antipsychotic agents such as risperidone, olanzapine, clozapine, quetiapine, and ziprasidone, little is known about the potential risks of teratogenicity or the potential effects in the neonate.

The risk of teratogenicity with benzodiazepines is not clear (108). Early studies, primarily with diazepam and chlordiazepoxide, suggested that first-trimester exposure may have led to malformations, including facial clefts, in some infants. Later studies showed no significant increases in specific defects or in the overall incidence of malformations (108). A recent meta-analysis of the risk of oral cleft or major malformations showed no association with fetal exposure to benzodiazepines in pooled data from co-hort studies, but a greater risk was reported on the basis of pooled data from case-control studies (109). In general, however, teratogenic risks are thought likely to be small with benzodiazepines (105). Near term, use of benzodiazepines may be associated with sedation in the neonate. Withdrawal symptoms resulting from dependence may also be seen in the neonate (108). As a result, if benzodiazepines are used during pregnancy, lorazepam is generally preferred (105).

ECT is also a potential treatment for severe mania or depression during pregnancy (110). In terms of teratogenicity, the short-term administration of anesthetic agents with ECT may present less risk to the fetus than pharmacological treatment options (111). The APA Task Force Report on ECT contains additional details on the use of ECT during pregnancy (110).

c) Prenatal monitoring.    Women who choose to remain on regimens of lithium, valproate, or carbamazepine during pregnancy should have maternal serum a-fetoprotein screening for neural tube defects before the 20th week of gestation, with amniocentesis as well as targeted sonography performed for any elevated a-fetoprotein values (105). Women should also be encouraged to undergo high-resolution ultrasound examination at 16-18 weeks gestation to detect cardiac abnormalities in the fetus. Since hepatic metabolism, renal excretion, and fluid volume are altered during pregnancy and the perinatal period, serum levels of medications should be monitored and doses adjusted if indicated. At delivery, the rapid fluid shifts in the mother will markedly increase lithium levels unless care is taken to either lower the lithium dose, ensure hydration, or both (112). Discontinuing lithium on the day of delivery is probably not necessary and may be unwise given the high risk for postpartum mood episodes and the greater risk of recurrence if lithium is discontinued in women with bipolar disorder (94,112).

d) Postpartum issues.    The postpartum period is consistently associated with a markedly greater risk for relapse into mania, depression, or psychosis. For women with bipolar disorder, the rate of postpartum relapse is as high as 50% (86,94). Women who have had severe postpartum affective episodes in the past are at highest risk to have another episode of illness after subsequent pregnancies. Despite a paucity of studies, it is generally considered that prophylactic medications such as lithium or valproate may prevent postpartum mood episodes in women with bipolar disorder (113). Also, since changes in sleep are common in the postpartum period, women should be educated about the need to maintain normal sleep patterns to avoid precipitating episodes of mania.

e) Infant medication exposure through breast-feeding.    All medications used in the treatment of bipolar disorder are secreted in breast milk in varying degrees, thereby exposing the neonate to maternally ingested medication (114). However, as with the risks of medications during pregnancy, risks of breast-feeding with psychotropic medications must be weighed against the benefits of breast-feeding (115,116). Because lithium is secreted in breast milk at 40% of maternal serum concentration, most experts have recommended against its use in mothers who choose to breast-feed (105). Fewer data on breast-feeding are available for carbamazepine and valproate. Although it is generally considered safe, potential risks should always be considered. Little is known about lamotrigine exposure in breast-fed neonates; however, levels in the infant may reach 25% of maternal serum levels (117). Consequently, the potential for pharmacological effects, including a risk for life-threatening rash, should be taken into consideration (118). With other psychotropic medications (including antipsychotics, antidepressants, and benzodiazepines), there are few reports of specific adverse effects in breast-feeding infants. Nonetheless, these drugs are found in measurable quantities in breast milk and could conceivably affect central nervous system functioning in the infant (118).

3. Cross-cultural issues
Culture can influence the experience and communication of symptoms of depression and mania. Underdiagnosis or misdiagnosis, as well as delayed detection of early signs of recurrence, can be reduced by being alert to specific ethnic and cultural differences in reporting complaints of a major mood episode. Specifically, minority patients (particularly African and Hispanic Americans) with bipolar disorder are at greater risk for being misdiagnosed with schizophrenia (119,120). This greater risk appears to result from clinicians failing to elicit affective symptoms in minority patients with affective psychoses (121).

Ethnicity and race must also be taken into consideration when prescribing medications, since ethnic and racial groups may differ in their metabolism of some medications (122,123). For example, relative to Caucasian patients, Chinese patients have a lower average activity of the cytochrome P-450 isoenzyme 2D6 (123). As a result, they typically require lower doses of antidepressants and antipsychotics that are metabolized by this enzyme (122). Similar deficits in average activity of the cytochrome P-450 isoenzyme 2C19 have been found in Chinese, Japanese, and Korean patients compared with Caucasians (123).

4. Children and adolescents
The prevalence of bipolar disorder in a community sample of children and adolescents was 1%; an additional 5.7% had mood symptoms that met criteria for bipolar disorder not otherwise specified (124). Although DSM-IV-TR criteria are used to diagnose bipolar disorder in childhood and adolescence, the clinical features of childhood bipolar disorder differ from bipolar disorder in adults. Children with bipolar disorder often have mixed mania, rapid cycling, and psychosis (125). Child and adolescent bipolar disorder is often comorbid with attention deficit and conduct disorders (126-128). For children and adolescents in a current manic episode, 1-year recovery rates of 37.1% and relapse rates of 38.3% have been reported (1,129). In a 5-year prospective follow-up of adolescents experiencing bipolar disorder, relapse rates of 44% were found (130). Despite the severity and chronicity of this disorder in children and adolescents and its devastating impact on social, emotional, and academic development, treatment research has lagged far behind that of adult bipolar disorder.

Although there is more information available about the use of lithium and divalproex in children and adolescents with bipolar disorder, other medication treatment options include atypical antipsychotics, carbamazepine, and combinations of these medications.

Treatment with a maintenance agent should continue for a minimum of 18 months after stabilization of a manic episode. There is evidence that ultimate stabilization takes a number of years (131). In addition, lithium discontinuation has been shown to increase relapse rates in adolescents with bipolar disorder: relapse occurred within 18 months in 92% of those who discontinued lithium versus 37% of those who continued lithium (132). Consequently, medication discontinuation should be done gradually at a time when there are no major anticipated stressors.

Psychiatric comorbidity may complicate the diagnosis and treatment of bipolar disorder in children and adolescents. The presence of ADHD, especially in children and adolescents, confounds the assessment of mood changes in patients with bipolar disorder. Early manifestations of mania and hypomania can be particularly difficult to distinguish from the ongoing symptoms of ADHD. Careful tracking of symptoms and behaviors is helpful. In addition, the presence of ADHD is associated with higher rates of learning disabilities, which should be addressed in treatment planning.

Youths with bipolar disorder are at greater risk for substance use disorders (133,134). Comorbid substance use has been shown to complicate the course of bipolar disorder and its treatment (135). Short-term treatment with lithium (136) and divalproex (137) may be useful in these conditions. However, in a 2-year follow-up of hospitalized manic adolescents, the bipolar disorder patients who continued to abuse substances had more manic episodes and poorer functioning than early-onset bipolar disorder patients who did not exhibit comorbid substance abuse. In contrast, cessation of substance use was associated with fewer episodes and greater functional improvement at the 4-year follow-up point (135).

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What about the "new" psychiatric medications?

Rye Hospital has always prided itself on educating its medical staff to use medications prudently. We are not given to "jumping in" with the "latest," simply because it's on the "market."

Thus, we have been circumspect when questions were raised about the serious side effects of some of the newer medications, such as the so-called "SSRIs," and the "atypical antipsychotics."

With the SSRIs, questions of increased suicidality, and with the atypicals, the disturbing and toxic side effects of diabetes and even pancreatitis are now noted here and abroad.

Therefore, at Rye, as indicated to do so by the Food and Drug Administration, doctors must give clear information to patient and family about the drugs being used and their possible negative effects. (See "Doctors Page".)

Recent Research Performed at Rye Hospital:

Construct Validation of Actigraphic Sleep Measures in Hospitalized Depressed Patients

Timothy G. Coffield, Ph.D.
Health Care Consultant
Palm Beach County, FL

Warren W. Tryon, Ph.D.

Department of Psychology
Fordham University

This study validated wrist actigraphic-measured sleep in depressed patients using construct validity by experimental intervention methods. The experimental participants were 18 patients hospitalized for major depression. Control participants were hospital staff. A 2-between (depressed patients vs. controls) × 2-within (pre- vs. post-) experimental design was used. Sleep was evaluated for 1 week, 7 nights, using wrist actigraphy on hospitalization and for a second week just prior to discharge. Clinical improvement was corroborated by statistically significant changes in the Beck Depression Inventory and the Inventory to Diagnose Depression. Sleep-onset latency, number of nighttime awakenings, minutes awake after sleep onset, and sleep efficiency all improved significantly as hypothesized. Minutes of sleep changed in the predicted direction but not significantly. Significant differences from control participants remained at discharge regarding minutes awake after sleep onset and sleep efficiency. These findings extend practice guidelines for actigraphy established by the Standards of Practice Committee (1995) of the American Sleep Disorders Association.

(Requests for reprints should be sent to Warren W. Tryon, Department of Psychology, Fordham University, Bronx, NY 10458–5198. E-mail: wtryon@fordham.edu)

2003

The Joint Commission on Accreditation of Healthcare Organizations conducted another of its triennial accreditation surveys of Rye Hospital Center on February 19-21, 2003.

The purpose of the survey was to evaluate the organization's compliance with nationally established Joint Commission standards to determine whether, and the conditions under which, accreditation should be awarded the organization.

As a result of the JCAHO survey, the hospital was granted its full three-year accreditation, with a score of 93.

CMS APPROVES!

In September, 2003, the Center for Medicaid and Medicare Services, of the US Department of Health and Human Services, granted full approval to the hospital after completion and response with the new "unannounced survey" process. The hospital was found to be in full compliance with the federal requirements for Conditions for Participation of Hospitals under Medicare.

9/15/2003

RYE HOSPITAL EXPANDS THE RAPID STABILIZATION SERVICE PROGRAM

The Rapid Stabilization Service is an ultra-short stay, intensive treatment program designed to maximize the use of all resources available to a qualified nursing facility and its residents.

Rye's senior and board-certified psychiatrists, and other psychiatrists regularly attending nursing home residents, will be able to participate in the Rapid Stabilization Service. Psychiatrists not presently on the Rye staff may apply for courtesy or full-staff privileges to ensure continuity in the care of their patients. Psychiatrists unable to follow the patient to Rye will receive interim patient-progress reports and, when the patient is referred back to them, the discharge plan.

1. The first requirement is screening of patients immediately upon admission to the nursing facility. In addition to their clinical skills, Rye's geriatric psychiatrists will use instruments designed to rate the intensity and duration of abnormalities in the patient's mood, thinking, perception and vegetative functioning. Nursing home psychiatrists not presently on the staff at Rye may contact any Rye geriatric-staff psychiatrist for assistance or collaboration in the diagnostic process.

2. Patients will be segregated into three distinct categories conforming with the latest American Psychiatric Association Diagnostic and Statistical Manual:

a. Depressive symptoms.

b. Depressive disorders.

c. No (or other) psychopathology.

3. The admission, nursing, and social service staffs of the nursing facility will assess the patient's recent history using a psychogeriatric rating scale. This is a highly reliable instrument in assessing orientation, behavior and ADL--noting changes in habits of dressing, bathing, personal hygiene, toileting, eating and mobility--and comparing them before and after admission.

4. As soon as a presumptive diagnosis is made, the psychiatrist will alert the nursing staff to observe the patient for several days to rule out factors reflecting the subject's adjustment to a strange environment.

5. The psychiatrist will coordinate the psychiatric treatment plan with the primary physician to rule out possible effects on the patient's mental state of other prescribed medications, including ""beta-blockers"" or other antihypertensives and analgesics, as well as certain antibiotics or steroids. As appropriate to the specific level of need, the psychiatrist will begin to treat the patient in the nursing facility. Depending on the severity and specificity of the patient's condition, the psychiatric treatment may include psychotropic medication.

6. Because studies demonstrate that diagnosis or even the initiation of antidepressants has little effect on the course of the depression, maintenance or improvement of ADL will be emphasized and integrated in the treatment plan, while the patient in the nursing facility receives other important aspects of medical workup.

7. Ideally, after ""bed-hold"" is assured, the psychiatrist may prescribe a short-term hospitalization in the Rapid Stabilization Service (RSS) at Rye. The purpose of the RSS is to organize the intensive treatment regimen affordable only at the higher levels of care offered by a behaviorally oriented psychiatric hospital.

8. Length of stay in the RSS is targeted at 10-to-18 days. The intensive treatment involves:

a. Medication adjustment to reduce psychomotor retardation.

b. Behavioral adaptation to group interaction.

c. Improvement in nutritional status.

d. Production of adequate sleep patterns.

e. Cultivation of ADL skills.

f. Formulation of an individualized post-discharge protocol for the patient's return to the nursing home and the nursing home psychiatrist.

9. After returning to the nursing facility, the patient would be seen at least weekly by the psychiatrist until reintegration and stability are assured, then at the frequency indicated. In addition, the behavioral skills learned by the patient at Rye would be reinforced regularly according to the discharge protocol.Many depressed patients referred to nursing homes by their families or personal physicians score as cognitively and physically healthier than those with clear physical disabilities. This has now proved to be more of a liability than an asset since it often obscures the underlying depressive process.

Because depression in the elderly has been shown to be a widespread, highly prevalent, potentially lethal, yet readily treatable condition of residents in nursing home populations, its resolution is imperative.

This would open up nursing home beds for more physically ill patients in need of the intensive treatment traditionally and ably offered by nursing homes.

The Behavioral Medicine Service at Rye Hospital Center
754 Boston Post Road, Rye New York 10580
(914) 967- 4567