Article on managing bipolar disorder in women who want to become pregnant or have an unplanned pregnancy.

Because bipolar disorder (manic-depressive illness) is a common and highly recurrent disorder requiring lifelong treatment, many women of childbearing age are maintained on mood stabilizers, usually lithium and the anticonvulsant Depakote (valproic acid).

Both drugs are teratogenic, so women with bipolar disease have typically been counseled to defer childbearing or abruptly stop their medications when they get pregnant. However, the discontinuation of lithium is associated with a high risk of relapse, and pregnancy does not protect women from relapsing. In a recent study, 52% of pregnant women and 58% of non-pregnant women had recurrences during the 40 weeks after stopping lithium (Am. J. Psychiatry, 157[2]:179-84, 2000).

There are no contraindications to lithium or Depakote use during the second and third trimesters. First-trimester exposure to Depakote is associated with a 5% risk of neural tube defects. Prenatal exposure to lithium in the first trimester is associated with an increased risk for cardiovascular malformations.

Although lithium is clearly teratogenic, the degree of risk has been previously overestimated. The report from the International Registry of Lithium- Exposed Babies almost 35 years ago estimated that the risk of cardiovascular malformations, most notably Ebstein's anomaly, associated with first-trimester exposure was increased by about 20-fold. But six later studies show that the risk is increased no more than 10-fold (JAMA 271[2]:146-50, 1994).

Because Ebstein's anomaly is so rare in the general population (about 1 in 20,000 births), the absolute risk of having a child with this malformation after first-trimester exposure to lithium is only about 1 in 1,000 to 1 in 2,000.

Managing Bipolar Disorder During Pregnancy

So how do you manage bipolar disease in women who want to become pregnant or have an unplanned pregnancy? Clinicians should not arbitrarily stop or continue mood stabilizers in these patients. The decision should be driven by both the severity of the illness and the patient's wishes; this requires a careful discussion with the patient about the relative risks of relapse and fetal exposure.

A reasonable approach in patients with a milder form of the illness, who may have had one episode in the distant past, is to discontinue the mood stabilizer while they are trying to get pregnant or when they become pregnant. They can resume the medication if they begin to show signs of clinical deterioration during pregnancy. This approach can pose a problem in women who take more than a few months to conceive, since the risk of relapse increases the longer a patient is off medication.

The best-case scenario in women with milder illness is to stay on the mood stabilizer while trying to get pregnant and to stop treatment as soon as they know they are pregnant. Women must be aware of their cycle pattern so they can stop the drug soon enough to avoid exposure during a critical time of organ development.

Going off medication maybe harder for those with a history of multiple episodes of cycling. We explain to such patients that it may be reasonable to stay on the mood stabilizer and assume a small risk to the fetus. If a woman on lithium decides to continue treatment, she should have a level II ultrasound at about 17 or 18 weeks' gestation to evaluate the fetal cardiac anatomy.

It's a more delicate situation when such a patient is stabilized on Depakote. Lithium is less teratogenic, so we often switch a woman on Depakote to lithium before she gets pregnant. That doesn't mean we never use Depakote during pregnancy. But when we do, we prescribe 4 mg of folate per day for about 3 months before they try to conceive and then throughout the first trimester because of data suggesting that this may minimize the risk of neural tube defects.

We don't discontinue or lower the dose of lithium or Depakote near the end of pregnancy or during labor and delivery because the incidence of any type of neonatal toxicity associated with peripartum exposure to these drugs is low--and bipolar women are at a five-fold increased risk of relapse in the postpartum period. This is why we also resume medication in women who have been off medication at about 36 weeks' gestation or 24-72 hours post partum.

Typically, bipolar women on lithium are counseled to defer breast-feeding because this drug is secreted into breast milk and there are a few anecdotal reports of neonatal toxicity associated with exposure to lithium in breast milk. Anticonvulsants are not contraindicated during lactation. Since sleep deprivation is one of the strongest precipitants of clinical deterioration in bipolar patients, we suggest that bipolar women defer breast-feeding, unless there is a clearly established plan to ensure she gets enough sleep.

About the author: Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston.

Source: Family Pratice News, Oct. 2000

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Researchers conclude that lithium maintenance provides a sustained protective effect against suicidal behavior in manic-depressive disorders, a benefit that has not been shown with any other medical treatment.

Can timely diagnosis and treatment of depression reduce the risk of suicide? Studies of treatment effects on mortality in major mood disorders remain rare and are widely considered difficult to carry out ethically. Despite close associations of suicide with major affective disorders and related comorbidity, the available evidence is inconclusive regarding for sustained reductions of suicide risk by most mood-altering treatments, including antidepressants. Studies designed to evaluate clinical benefits of mood-stabilizing treatments in bipolar disorders, however, provide comparisons of suicidal rates with and without treatment or under different treatment conditions. This emerging body of research provides consistent evidence of reduced rates of suicides and attempts during long-term treatment with lithium. This effect may not generalize to proposed alternatives, particularly carbamazepine. Our recent international collaborative studies found compelling evidence for prolonged reduction of suicidal risks during treatment with lithium, as well as sharp increases soon after its discontinuation, all in close association with depressive recurrences. Depression was markedly reduced, and suicide attempts were less frequent, when lithium was discontinued gradually. These findings indicate that studies of the effects of long-term treatment on suicide risk are feasible and that more timely diagnosis and treatment for all forms of major depression, but particularly for bipolar depression, should further reduce suicide risk.

INTRODUCTION

Risk of premature mortality significantly increases in bipolar manic-depressive disorders.(1-12) Mortal risk arises from very high rates of suicide in all major affective disorders, which are at least as great in bipolar illness as in recurrent major depression.(1, 2, 13-16) A review of 30 studies of bipolar disorder patients found that 19% of deaths (range in studies from 6% to 60%) were due to suicide.(2) Rates may be lower in never-hospitalized patients, however.(6, 11, 12) In addition to suicide, mortality is probably also increased due to comorbid, stress-related, medical disorders, including cardiovascular and pulmonary diseases. (3-5, 7, 10) High rates of comorbid substance use disorders contribute further to both medical mortality and to suicidal risk (11, 17), especially in young persons (18), in whom violence and suicide are leading causes of death.(11, 12, 19)

Suicide is strongly associated with concurrent depression in all forms of the common major affective disorders.(2, 9, 20, 21) Lifetime morbid risk for major depression may be as high as 10%, and lifetime prevalence of bipolar disorders probably exceeds 2% of the general population if cases of type II bipolar syndrome (depression with hypomania) are included. (2, 22, 23) Remarkably, however, only a minority of persons affected with these highly prevalent, often lethal, but usually treatable major affective disorders receive appropriate diagnosis and treatment, and often only after years of delay or partial treatment. (8 ,9, 22, 24-28) Despite grave clinical, social, and economic effects of suicide, and its very common association with mood disorders, specific studies on the effects of mood-altering treatments on suicidal risk remain remarkably uncommon and inadequate to guide either rational clinical practice or sound public health policy.(7, 8, 11, 12, 22, 29, 30)

In view of the clinical and public health importance of suicide in manic-depressive disorders, and the rarity of evidence proving that modern mood-altering treatments reduce suicide rates, an emerging body of research has been reviewed. It indicates a significant, sustained, and possibly unique reduction of suicidal behavior during long-term treatment with lithium salts. These important effects have not been demonstrated with other mood-altering treatments.

THERAPEUTICS RESEARCH IN SUICIDE

Despite broad clinical use and intensive study of antidepressants for four decades, evidence that they specifically alter suicidal behavior or reduce long-term suicidal risk remains meager and inconclusive.(9, 11, 17, 31-37) The introduction of selective serotonin reuptake inhibitors (SSRIs) and other modern antidepressants that are much less toxic on acute overdose than older drugs appears not to have been associated with a decrease in suicide rates.(34, 38) Instead, their introduction may have been associated with a shift toward more lethal means of self-destruction.(39) We found only one report of a significantly lower rate of suicide in depressed patients treated with antidepressants compared to placebo (0.65% vs 2.78% per year), with an even lower rate with an SSRI than with other antidepressants (0.50% vs 1.38% per year).(37) Nevertheless, suicide rates during antidepressant treatment in that study were far greater than the general population rate of 0.010% to 0.015% per year, uncorrected for persons with mood disorders and other illnesses associated with increased suicide rates.(40)

Bipolar depression accounts for much or most of the time one is stricken with bipolar disorder (24) and can be disabling or fatal.(2, 7, 11, 12) Remarkably, however, the treatment of this syndrome remains much less studied than depressive to manic, agitated or psychotic unipolar major depression.(24, 38, 41) Indeed, bipolarity is typically a criterion for exclusion from studies of antidepressant treatment, apparently to avoid risks of switching from depressive to manic, agitated or psychotic phases when patients are not protected with lithium or another mood-stabilizing agent.(38)

Reasons for the rarity of studies of the effects of modern psychiatric treatments on suicide rates are not entirely clear. Therapeutic research on suicide is appropriately constrained ethically when fatality is a potential outcome, and particularly when discontinuation of ongoing treatment is required in a research protocol. Treatment discontinuation is increasingly recognized as being followed by at least temporary, sharp increases in morbidity that may exceed the morbid risk associated with untreated illness. This evidently iatrogenic phenomenon has been associated with discontinuation of maintenance treatment with lithium (42-46), anti-depressants (47), and other psychotropic agents.(44, 48) Mortality can also increase following treatment discontinuation. (9, 11, 21, 22) Such reactions can complicate clinical management. Moreover, they may also confound many research findings in that typically reported "drug vs. placebo" comparisons may not represent straightforward contrasts of treated vs untreated subjects when placebo conditions represent discontinuation of an ongoing treatment.

Avoiding such risks, most studies of treatment effects on suicide have been naturalistic or have examined suicidal behavior post-hoc as an unintended outcome of controlled treatment trials. Such studies have provided evidence that maintenance treatment with lithium is associated with a strong, and possibly unique, protective effect against suicidal behavior in major affective disorders, and particularly in bipolar syndromes. (6, 8, 11, 12, 21, 22, 49-56) Moreover, lithium's protective effect may extend more broadly to all causes of mortality in these disorders, although this possibility remains much less studied. (2, 3, 5, 7)

SUICIDE RATES ON AND OFF LITHIUM

We recently evaluated all available studies of lithium and suicide since the emergence of long-term lithium maintenance treatment in manic depressive disorders in the early 1970s. Studies were identified by computerized literature searches and cross-referencing from publications on the topic, as well as by discussing the aims of the study with colleagues who have conducted research on lithium treatment or who may have had access to unpublished data on suicide rates in bipolar disorder patients. We sought data permitting estimates of rates of attempted or completed suicides in bipolar patients or mixed samples of patients with major affective disorders that included bipolar manic-depressives. Suicide rates during maintenance lithium treatment were compared with rates after discontinuation of lithium or in similar untreated samples when such data were available.

Suicide rates during long-term lithium treatment were determined for each study, and, when available, rates for patients discontinued from lithium or for comparable patients not treated with a mood stabilizer were also determined. Suicide rates during lithium treatment were not significantly greater with larger numbers of subjects or longer follow-up. However, many of the available reports were flawed in one or more respects. Limitations included: (1) a common lack of control over treatments other than lithium; (2) incomplete separation by diagnosis or provision of separate rates for suicide attempts and completions in some studies; (3) a lack of comparisons of treated and untreated periods within subjects or between groups; (4) study of fewer than 50 subjects/treatment conditions despite the relatively low frequency of suicide; (5) inconsistent or imprecise reporting of time-at-risk (the amount of time the patient was absent); and (6) selection of patients with previous suicide attempts that may show bias toward increased suicide rates in some studies. Some of these deficiencies were resolved by contacting authors directly. Despite their limitations, we believe that the available data are of sufficient quality and importance to encourage further evaluation.

Table 1 summarizes available data concerning rates of suicides and attempts among manic-depressive patients on or off lithium, based on previously reported (6) and new, unpublished meta-analyses. The results indicate an overall reduction of risk by nearly seven fold, from 1.78 to 0.26 suicide attempts and suicides per 100 patient-years at risk (or percent of persons/year). In another more recent, quantitative meta-analysis (L.T., unpublished, 1999), we evaluated fatality rates ascribed to suicide in the same studies as well as in additional previously unreported data kindly provided by international collaborators. In the latter analysis, based on results from 18 studies and more than 5,900 manic-depressive subjects, we found a similar reduction of risk from a suicide rate averaging 1.83 ± 0.26 suicides per 100 patient-years in patients not treated with lithium (either after discontinuing or in parallel groups not given lithium) to 0.26 ± 0.11 suicides per 100 patient-years in patients on lithium.

IMPLICATIONS OF FINDINGS

The present findings derived from the research literature on lithium and suicide risk indicate substantial protection against suicide attempts and fatalities during long-term lithium treatment in patients with bipolar manic-depressive disorders, or in mixed groups of major affective disorder subjects that included bipolar patients. While this evidence is strong and consistent overall, the relative infrequency of suicide and limited size of many studies required pooling of data to observe statistically significant effect that was not found in several individual studies. Large samples and lengthy times-at-risk, or pooling of data across studies, are likely to be required in future studies of treatment effects on suicide rates.

It is also important to emphasize that the observed, pooled, residual risk of suicides while on lithium, though much lower than without lithium treatment, is still large, and greatly exceeds general population rates. The average suicide rate during lithium maintenance treatment, at 0.26% per year (Table 1), is more than 20 times greater than the annual general population rate of about 0.010% to 0.015%, which also includes suicides associated with psychiatric illnesses.(11, 40) The evidently incomplete protection against suicide associated with lithium treatment may reflect limitations in the effectiveness of the treatment itself and, very likely, potential noncompliance to long-term maintenance therapy.

Since suicidal behavior is closely associated with concurrent depressive or dysphoric mixed states in bipolar disorder patients (9, 11, 20), it is likely that residual risk for suicide is associated with incomplete protection against recurrences of bipolar depressive or mixed mood states. Lithium has traditionally been considered to provide better protection against mania than against bipolar depression.(27, 38) In a recent study of more than 300 bipolar I and II subjects, we found that depressive morbidity was reduced from 0.85 to 0.41 episodes per year (a 52% improvement) and time ill was reduced from 24.3% to 10.6% (a 56% reduction) before vs during lithium maintenance treatment.(23) Improvements in mania or hypomania were somewhat larger, at 70% for episode rates and 66% for percentage of time manic, with even greater improvement in hypomania in type 11 cases (84% fewer episodes and 80% less time hypomanic). Corresponding suicide rates fell from 2.3 to 0.36 suicide attempts per 100 patient-years (an 85% improvement) during vs before lithium maintenance treatment. (9, 20) The present findings indicate an 85% to crude sparing of completed suicides and attempts (1.78 to 0.26% per year; see Table 1). These comparisons suggest that protective effects of lithium rank: suicide attempts or suicides ³ hypomania>mania>bipolar depression. Since suicide is closely associated with depression (11, 20), it follows that better protection against bipolar depression must be a key to limiting suicidal risk in bipolar disorders.

It is not clear whether reduction of suicide rates during lithium maintenance reflects simply the mood-stabilizing effect of lithium, or if other properties of lithium also contribute. In addition to protection from recurrences of bipolar depressive and mixed-mood states closely associated with suicidal behavior, important associated benefits of lithium treatment possibly also contribute to reduction of suicide risk. These may include improvements in overall emotional stability, interpersonal relationships and sustained clinical follow-up, vocational functioning, self-esteem, and perhaps reduced comorbid substance abuse.

An alternative possibility is that lithium may have a distinct psychobiological action on suicidal and perhaps other aggressive behaviors, possibly reflecting serotonin-enhancing actions of lithium in limbic forebrain. (38, 57) This hypothesis accords with growing evidence of an association between cerebral deficiency of serotonin functioning and suicidal or other aggressive behaviors. (58-59) If lithium protects against suicide through its central serotonergic activity, then proposed alternatives to lithium with dissimilar pharmacodynamics may not be equally protective against suicide. Specifically, mood-stabilizing agents that lack serotonin enhancing properties, including most anti-convulsants (27, 38), might not protect against suicide as well as lithium. It would be unwise clinically to assume that all putative mood-stabilizing agents provide similar protection against suicide or other impulsive or dangerous behaviors.

For example, findings from recent reports from a multicenter European collaborative study challenge the assumption that all effective mood-altering treatments have a similar impact on suicide rates. This study found no suicidal acts among bipolar and schizoaffective disorder patients maintained on lithium, whereas carbamazepine treatment was associated with a significantly higher rate of suicides and suicide attempts in 1% to 2% of subjects per year-at-risk. (60, 61) Patients assigned to carbamazepine had not been discontinued from lithium (B. Müller-Oerlinghausen, written communication, May 1997), which might otherwise have increased risk iatrogerically. (8, 42-46) A similar rate of suicide attempts to that found with carbamazepine in bipolar patients was also found among patients with recurrent unipolar depression who were maintained long-term on amitriptyline, with or without a neuroleptic. (60, 61) These provocative observations regarding carbamazepine and amitriptyline indicate the need for specific assessments of other proposed alternatives to lithium for their potential long-term protection against suicidal risk in bipolar disorder patients.

Several drugs are used empirically to treat bipolar disorder patients, although they remain largely untested for long-term, mood-stabilizing effectiveness. In addition to carbamazepine, these include the anticonvulsants valproic acid, gabapentin, lamotrigine, and topiramate. Sometimes calcium channel-blockers, such as verapamil, nifedipine, and nimodipine, are employed, and newer, atypical antipsychotic agents including clozapine and olanzapine are increasingly used to treat bipolar disorder patients, encouraged in part by an assumption that risk of tardive dyskinesia is low. The potential antisuicide effectiveness of these agents remains unexamined. An exception to this pattern is clozapine, for which there is some evidence of antisuicidal and perhaps other antiaggressive effects, at least in patients diagnosed with schizophrenia. (62) Clozapine is sometimes used, and may be effective, in patients with otherwise treatment-unresponsive major affective or schizoaffective disorders (63, 64), but its antisuicidal effects in bipolar disorder patients have yet to be investigated. Contrary to the hypothesis that serotonergic activity may contribute to antisuicidal effects, clozapine has prominent antiserotonin activity, particularly at 5-HT2A receptors (65, 66), suggesting that other mechanisms may contribute to its reported antisuicidal effects.

EFFECTS OF DISCONTINUING LITHIUM ON SUICIDE RISK

Another factor to consider in interpreting the findings pertaining to effects of lithium treatment on suicide rates is that most of the studies analyzed involved comparisons of suicide rates during vs after discontinuing long-term lithium treatment. In a recent international collaborative study, we found that clinical discontinuation of lithium maintenance treatment was associated with a sharp increase in suicidal risk in a large, retrospectively analyzed sample of bipolar I and II patients.(8, 9, 20, 21, 46) Rates of suicide attempts had decreased by more than six-fold during lithium maintenance treatment, compared to years between onset of illness and the start of sustained maintenance treatment (Table 2). In these patients, nearly 90% of life-threatening suicide attempts and suicides occurred during depressive or dysphoric mixed-mood states, and previous severe depression, prior suicide attempts, and younger age at onset of illness significantly predicted suicidal acts.

In striking contrast, after discontinuing lithium (typically at the patient's insistence following prolonged stability) rates of suicides and attempts increased 14-fold overall (Table 2). In the first year after discontinuing lithium, affective illness recurred in two thirds of patients, and rates of suicide attempts plus fatalities increased 20-fold. Suicides were nearly 13 times more frequent after discontinuing lithium (Table 2). Of note, at times later than the first year off lithium, suicide rates were virtually identical to those estimated for the years between onset of illness and the start of sustained lithium maintenance. These findings strongly suggest that lithium discontinuation carries added risk, not only of early recurrence of affective morbidity, but also of a sharp increase in suicidal behavior to levels well in excess of rates found before treatment, or at times later than a year after discontinuing treatment. These increased suicidal risks may be related to a stressful impact of treatment discontinuation itself that may have contributed to most of the contrasts shown in Table 1 between subjects treated with lithium vs subjects who discontinued lithium use.(8)

If stopping lithium is followed by added suicide risk associated with recurrence of bipolar depression or dysphoria, then slow discontinuation of treatment may reduce the incidence of suicide. Encouraging preliminary findings indicated that, after gradual discontinuation of lithium over several weeks, suicidal risk was reduced by half (Table 2).(9, 21) The median time to first recurring episodes of illness was increased an average of four times after gradual vs rapid or abrupt discontinuation of lithium and the median time to bipolar depression was delayed by about threefold. (8, 45, 46) The apparent protective effect of gradually discontinuing lithium against suicidal risk may reflect the highly significant benefits of gradual discontinuation against early recurrences of affective episodes as a key intervening variable.(8).

About the authors: Ross J. Baldessarini, M.D., Leonardo Tondo, M.D., and John Hennen, Ph.D., of the Bipolar & Psychotic Disorders Program of McLean Hospital, and the International Consortium for Bipolar Disorder Research. Dr. Baldessarini is also Professor of Psychiatry (Neuroscience) at Harvard Medical School and Director of the Laboratories for Psychiatric Research and the Psychopharmacology Program at McLean Hospital.

Source: Primary Psychiatry. 1999;6(9):51-56

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Researchers are working on a physical test to pin down diagnosis of ADHD.

Boston Life Sciences, Inc. released details of a human clinical study demonstrating that its diagnostic radioimaging agent, Altropane™, has detected an abnormal elevation in the number of dopamine transporters (DATs) in the brains of subjects with longstanding Attention Deficit Hyperactivity Disorder (ADHD). The study appears in the current issue of the prestigious British medical journal The Lancet.

Dr. Alan Fischman, senior author of The Lancet study, and Chief of Nuclear Medicine at the Massachusetts General Hospital stated, "the findings in this study are very significant, and demonstrate that Altropane potentially could be of great value in establishing the existence of an objective biological abnormality in ADHD."

Upon reviewing the study, psychiatrist Edward Hallowell, M.D, nationally recognized expert in ADHD and author of the book Driven to Distraction, stated, "Altropane is the most promising development I've seen in a long time in terms of our coming up with an actual physical test that could help us pin down the diagnosis of ADHD."

"There is currently great concern among parents, educators and health professionals regarding the accuracy of current psychosocial criteria used to diagnose ADHD, particularly in children, and the related problem of inappropriate use of potentially addictive stimulant medication for this poorly-defined condition. If the positive results obtained in our initial study in adults are further confirmed in children, we expect that Altropane will prove to be of immense value in helping health professionals and parents to deal with these important issues. Given its potential use to objectively diagnose ADHD in students as well as young adults who exhibit symptoms of inattentiveness and hyperactivity, Altropane can also provide a definitive basis for the use of medication in those patients who might otherwise be reluctant to initiate drug therapy," stated Marc Lanser, MD, Chief Scientific Officer of BLSI.

John Heavener, Chief Executive Officer of CHADD, the nation's leading advocacy organization dealing with ADHD stated, "Altropane is potentially a valuable tool in reinforcing the diagnosis of the ADHD, and in providing the public with proof the disorder exists. We receive 200 to 300 calls everyday asking about the diagnosis and treatment of ADHD and we are encouraged that Altropane may be a meaningful tool in advancing the science used to diagnose the disorder."

"To our knowledge, this is the first clinical study to demonstrate that there is a measurable biochemical abnormality in patients with ADHD. In this trial, adult patients with expertly-diagnosed, longstanding ADHD underwent Altropane-SPECT brain scans. In the scan, a Striatal Binding Potential (SBP) was calculated for each patient. The SBP is an indirect measure of the quantity of dopamine transporters (DATs) in the brain. Each and every ADHD patient had a SBP that was at least two standard deviations above the mean SBP of age-matched controls. These results demonstrated that abnormal levels of the DAT are directly associated with the clinical symptoms of ADHD in this patient group," added Dr. Lanser.

Altropane is a small molecule invented by researchers at Harvard and the Massachusetts General Hospital that binds with extremely high affinity and specificity to the DAT. Consequently, the amount of Altropane taken up by the brain is directly proportional to the number of DATs that are present in any given area of the brain. In Parkinson's Disease (PD), there is a marked decrease in the number of DATs in the striatal region of the brain. As a result, Altropane uptake is substantially diminished. This marked decrease in Altropane uptake in PD is the basis for BLSI's diagnostic test for early PD. For this application, Altropane is now in a Phase III trial and if successfully completed, will be submitted for marketing approval next year. Conversely, as now suggested by The Lancet study, ADHD appears to be associated with an excess number of DATs in this same region and thus Altropane has the potential to prove to be a powerful diagnostic for ADHD as well.

ADHD is the most commonly diagnosed behavioral disorder in children and is the fastest growing psychiatric disorder in adults. Since 1990, the total number of American children diagnosed with ADHD has risen from 900,000 to over 5.5 million, and the use of stimulant medication such as Ritalin" has increased 700% in the same period. ADHD is currently diagnosed according to a set of behavioral criteria defined in the Diagnostic and Statistical Manual (DSM) used by psychiatrists. However, it has not been possible to validate these criteria against an objective biological standard, since such a standard has never been established and does not currently exist. Consequently, the DSM criteria have generated widespread concern and, in the view of many critics, often are misapplied and misinterpreted. The lack of a clear-cut, demonstrated biological basis for ADHD has led to a great deal of confusion concerning the diagnosis of ADHD and has even provoked skepticism regarding the very existence of the disorder.

"With 5-10% of approximately 55 million school-age children currently diagnosed with some form of ADHD, roughly 1.5 million initial visits for ADHD per year, and with approximately 1.5 million adults diagnosed with ADHD, the Company believes that Altropane has the potential, if approved, to become one of the largest selling radio-pharmaceutical diagnostics ever developed. We hope to initiate Phase II/III testing for the diagnosis of ADHD early in 2000. The clinical protocol for the ADHD study is currently under review by radioimaging and ADHD experts at the Massachusetts General Hospital and Children's Hospital at the University of Pennsylvania," stated David Hillson, CEO of BLSI."

Source: Press Release from Boston Life Sciences Inc. Please visit their web site for more information.

CBT has been proven to help patients with anxiety disorders confront their fears.

Clinicians who use cognitive-behavioral therapy (CBT) to help patients with anxiety disorders have more treatment success than clinicians who don't, suggest the results of a recent study.

In the study, 165 adults with anxiety disorders, including phobias and panic problems, sought treatment through The Synton Group, a managed behavioral health organization in Lansing, Mich. Of that number, 86 were treated by practitioners with specialized training in cognitive-behavioral therapy (CBT), and they proved to have lower rates of anxiety disorders relapse than others treated by non-CBT practitioners.

CBT clinicians also indicated that their patients had lower levels of anxiety on release from treatment. They typically treated their patients in six sessions, two fewer than their generalist colleagues used.

The CBT specialists were 18 doctoral-level psychologists and two master's-level providers. They indicated that they typically use such CBT techniques as desensitizing patients to the triggers of anxiety, and requiring them to confront their fears. The generalist group of practitioners, including 13 doctoral-level psychologists and 14 master's-level providers, said they used more traditional psychotherapy techniques that delve at what underlies anxiety.

In the two years following treatment, twice as many non-CBT patients as CBT patients--39 percent versus 19 percent--returned for further treatment, despite having had more treatment sessions initially. The study's author, psychologist Rodney C. Howard, PhD, describes that finding as "impressive" and claims it points to CBT's superiority.

"Based on this study, I believe that more clinicians should get cognitive behavioral training to treat anxiety," says Howard, noting that some, but not all, clinical doctoral programs provide it. "With managed care moving toward evidence-based treatment, it's more important to use interventions with demonstrated effectiveness."

Howard admits, however, to a limitation in his study, published in the October issue of Professional Psychology: Research and Practice (Vol. 30, No. 5, p. 470-473). Patients rated their own anxiety levels before treatment, while their therapists reported on those levels afterwards.

Still, "you have to accept some limitations in the real world," says Howard. "I wanted to see what actually happens in practice."

Source: APA Monitor, VOLUME 30, NUMBER 11 December 1999.

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Diagnosis of ADHD in preschoolers called into question and worries abound that doctors are prescribing stimulant medications for ADHD to preschoolers when the drugs have never been tested on very young children.

Children age three and under are being diagnosed with attention-deficit hyperactivity disorder (ADHD), in the absence of clear guidelines for this age group, and more than half of these children receive psychotropic medication, according to a report published in the October issue of the Archives of Pediatrics and Adolescent Medicine.

Dr. Marsha D. Rappley and colleagues, from Michigan State University in East Lansing, reviewed the medical claims records of 223 children who had been diagnosed with ADHD at or before the age of 3 years. More than one fourth had been diagnosed at or before the age of 2 years. Boys comprised 79.8% of the sample and 68.2% were white.

Comorbid conditions common among older children with ADHD were reported in 44% of the subjects, most commonly language and cognitive development problems. Other medical conditions were reported in 41%. Forty percent of the children were treated for physical injuries over the 15-month study period.

"These little children clearly have multiple problems, both in mental health and in chronic health," Dr. Rappley said in an interview. "I think primary care physicians want to address their urgent needs, but they don't have the information they need."

Psychological treatment was provided for only 27% of the children.

Psychotropic medications were given to 57%, most frequently methylphenidate and/or clonidine. Just over one third of children receiving medication took two or three psychotropic drugs simultaneously, with thirty different combinations of drugs used. Close to half of the children taking medications took from two to six different drugs over time.

Of particular concern, the authors comment, is that "... the extreme variation in the use of psychotropic medications suggests haphazard use at worst and uninformed use at best." They note that most of the drugs used have not been tested for safety and efficacy in very young children, either singly or in combination.

"When we see 22 different medications used in almost more ways than we could count," said Dr. Rappley, "... this reflects that we don't have guidance on how to use these medications and whether these are the best treatments for very young children."

"As professionals, we need to have a way of describing these children and getting appropriate services for them," she added. "Right now, we don't know how to do that."

Sources:

• Archives of Pediatrics and Adolescent Medicine (Arch Pediatr Adolesc Med 1999;153:1039-1045).

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©1999 The Disability News Service, Inc. by Leye Jeannette Chrzanowski
Wed, Oct 13, 1999

When Joseph A. Rogers, the executive director of the Philadelphia-based Mental Health Consumer's Self Help Clearinghouse (MHCSHC), was asked to review a copy of a chapter in the U.S. Surgeon General's report on mental health labeled "draft," he was shocked to read that electroconvulsive therapy (ECT) is regarded as a safe and effective treatment for depression.

Generally, such reports from the surgeon general are regarded as state of the art research, and are frequently cited as authoritative sources in media reports and professional journals. According to Rogers, at least the ECT section of the draft report on mental health fails to measure up to previous surgeon general reports on smoking and nutrition.

Outraged by the contents of the draft, MHCSHC issued an Internet alert in late September, warning that ECT's efficacy and safety have not been confirmed as stated in the draft report. The alert urged people to contact the surgeon general because the report endorsing ECT would be published later this year if its contents remained unchallenged. The result? The alert garnered national and international media attention. The New York Times, the Newark Star Ledger and Reuters news agency published articles about the draft report, and the office of the surgeon general was swamped by faxes from angry advocates denouncing the endorsement of ECT.

"I hope you understand that is not the surgeon general's draft report, said Damon Thompson a spokesman for the office of the surgeon general, when interviewed on October 12. It is one section of a small portion of proposed language that was given to a person for peer review, asserted Thompson. There is no report yet, and we're still very much in the process of reviewing and revising.

You know what it's like when you turn on the light in a room full of cockroaches and they scurry for cover? That's what it's like, says Rogers, who also questions the limited and questionable sources cited in the document.

The most frequently cited sources were Richard D. Weiner, M.D., Ph.D. and Andrew D. Krystal, M.D. Weiner heads Duke University Medical Center's Electroconvulsive Therapy Service and the American Psychiatric Association (APA) Task Force on ECT, which petitioned the Food and Drug Administration to lower its classification of ECT machines in 1982. Krystal, director of Duke's Sleep Disorder Center, received $150,036 in funding from the National Institutes of Mental Health (NIMH) in fiscal year 1998 to conduct research on improving ECT's effectiveness.

Clearly, the surgeon general's office simply did not do its homework, since there is a vast quantity of material that indicates that ECT is not safe, states the MHCSHC alert.

Rogers further asserts that the committee members who prepared the document cite old recycled information and ignore numerous sources which contradict the position that ECT is safe. They were asleep at the switch on putting out a cutting edge document for the surgeon general, says Rogers. He adds the surgeon general should be angry at the committee for turning out "sloppy work."

A NIMH fact sheet on depression posted on the federal agency's Internet Web site on April 13, 1999 also endorses ECT as one of the most effective treatments for depression. The fact sheet states:

Eighty to ninety percent of people with severe depression improve dramatically with ECT. ECT involves producing a seizure in the brain of a patient under general anesthesia by applying electrical stimulation to the brain through electrodes placed on the scalp.

Repeated treatments are necessary to achieve the most complete antidepressant response. Memory loss and other cognitive problems are common, yet typically short-lived side effects of ECT. Although some people report lasting difficulties, modern advances in ECT technique have greatly reduced the side effects of this treatment compared to earlier decades. NIMH research on ECT has found that the dose of electricity applied and the placement of electrodes (unilateral or bilateral) can influence the degree of depression relief and the severity of side effects.

Yet, the above assertion that the side effects of ECT are short-lived, and that ECT is safe, as stated in the surgeon general's draft document, appear to contradict the Electroconvulsive Therapy Background Paper published in 1998 by U.S. Department of Health and Human Services (HHS). The paper states that in 1985 the National Institute of Mental Health Consensus Development Conference on ECT identified five priority research tasks, but thirteen years later, many were not completed.

While many studies of ECT have been undertaken since the 1985 Consensus Development Conference on ECT, the issues regarding brain damage and memory loss have not yet been fully explored or understood, concludes the 1998 HHS document.

next: ECT: Sham Statistics, the Myth of Convulsive Therapy, and the Case for Consumer Misinformation
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WESTPORT, Oct 13 1999 (Reuters Health) - The vast majority of patients who undergo electroconvulsive therapy report that they are satisfied with its results.

"Many people assume that electroconvulsive therapy is something that is done despite the patient and their family preferring other treatment," investigator Dr. Lois E. Krahn, of Mayo Clinic Rochester in Minnesota, said in an interview with Reuters Health. On the contrary, she said, patients responding to a recent survey "...for the most part...were satisfied with their treatment."

Dr. Krahn and colleagues at the clinic surveyed a consecutive series of 24 psychiatric inpatients immediately after and 2 weeks after electroconvulsive therapy to determine their satisfaction with the procedure. The team used a modified version of the survey to investigate attitudes toward electroconvulsive therapy in 24 psychiatric outpatients who had never received the treatment.

Dr. Krahn told Reuters Health that all electroconvulsive therapy-treated patients had undergone prior pharmacologic therapy with either a poor response or unacceptable rate of side effects.

Of the treated patients, 91% responded "mostly true" or "definitely true" to the statement "I am glad that I received [electroconvulsive therapy]," Dr. Krahn and colleagues report in the October issue of Mayo Clinic Proceedings.

Those positive attitudes toward the procedure persisted for at least 2 weeks. Patients who reported being satisfied with the treatment were generally younger than dissatisfied patients and had attained higher levels of education. Treated patients had better attitudes toward electroconvulsive therapy than did controls who had never received such treatment.

"The degree of satisfaction may be surprising to the public and nonpsychiatric clinicians as well as to psychiatrists who are ambivalent about [electroconvulsive therapy]," the researchers write. Dr. Krahn acknowledged in the interview with Reuters Health that she, too, was "pleasantly surprised" by the proportion of patients who were satisfied with electroconvulsive therapy, although she had anticipated that many patients would be satisfied

The investigators note in the journal that further research is needed to assess satisfaction with electroconvulsive therapy over a longer term and to examine satisfaction in patients who are cognitively impaired.

In the meantime, Dr. Krahn told Reuters Health, she plans to use the new data when she counsels patients considering electroconvulsive therapy. Together with other information on the procedure, the new findings may aid patients in making informed decisions about electroconvulsive therapy, she believes.

Mayo Clin Proc 1999;74:967-971.

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I had an interesting and humorous experience with God while meditating. First off, let me just say I have never really meditated in any kind of serious or consistent way. I'm not very good at it. It's been a struggle for me to quiet my mind and I was never quite sure of its purpose. I couldn't quite grasp the concept of doing something with no expectations or goals.

"Like waves rolling up a beach to stillness."

I've read how great and helpful meditating has been for many people. I wanted to experience what they were experiencing even though I wasn't exactly sure what that was! Here's what happened.

I laid down in a recliner, closed my eyes and began focusing on taking deep breaths. As I became more and more relaxed, I became less aware of my body. I can't say my mind was completely quiet. Thoughts were there but they would drift away and become elongated like a wave rolling up the beach to stillness. I focused on those quiet moments between my thoughts trying to stretch them out in time. Throughout the mediation I would see things. Mostly shapes, dark purple clouds, flashes of light, it was almost psychedelic. I tried to focus on the shapes but as soon as I would, they would evaporate into the mist.

In my mind's eye I looked over and God was sitting on our couch. He was this guy in his mid-fifties with speckled gray and brown hair, beard, and wearing this white robe. The typical robe God is portrayed as wearing in a lot of religious imagery. But this guy was different. He was very relaxed and laid back. He was kinda slouched down with his arms resting on the back of the couch and his legs were crossed. He looked like any average Joe relaxing on a Sunday afternoon watching football. AND.I could have sworn I saw blue jeans peaking out from under his robes! I chuckled to myself thinking how different this image was from how I was raised to believe God would appear.

When he looked over at me we shared one of those "friend moments." You know the kind where you look at each other and it feels like you're sharing something special and secret between the two of you. I felt the connection. We both smiled knowingly at each. It was such a warm, familiar, and comfortable feeling.

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I let the image go and went back to "trying to meditate" which I thought meant not thinking or seeing anything. But another image appeared in my mind. I saw myself sitting in the classic lotus position, crossed legged, straight-backed with my arms outstretched resting on my knees, my thumbs and forefingers gently meeting. I tried to imagine what those "yogis" must be experiencing when in this pose. I so badly wanted to experience this place of "oneness" so many gurus reference in their descriptions.

Again, I looked over in my mind's eye to the couch. God was sitting there in the exact same lotus position I imaged myself to be sitting. It's almost like he was pantomiming or mocking me, but in a very loving way! He opened one of his eyes to see if I was looking. When our gazes met, we both busted out laughing.

Without opening his mouth to speak, and with a hint of remaining laughter in his voice(?) he said to me, "Jenn, you don't have to meditate like other people, whatever way you mediate IS the right way for you. It's not about sitting in the right position or exercising the correct technique, it's about quieting and slowing down your body and mind enough to create an open space. In that space you'll hear the pin drop that is me."

His style of communicating this message was absolutely perfect. He was so gentle. His use of humor defused the stress and worry I generally feel regarding "doing it right." Perhaps that's what made the situation so funny to me.

Upon reflection I realized how often I have look to others to tell me the "proper" or "correct" way to go about living life. Most of my life I've assumed there was one right way to do things and I desperately wanted to know what that way was. It felt like I had missed an important memo from the front office. Everyone else received it, but not me and since then I've been scrambling to catch up with what everyone else knows.

After this experience I'm much more inclined to ask myself "what do I think? What do I believe? Is this true for me?" I no longer take what others say as "the law." I question everything and find my own answers. I'm still an avid reader but authors' words are no longer cut in stone. I am now the final gateway to answers.

Thank you God for approaching me in such a fun and clear way!

next: Dialogue With God On Money~ back to: My Articles: Table of Contents

Documentary broadcast on Showtime, Sept. 13, 1999. Directed by Robert Zemeckis.

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Both genetics and structural brain makeup play a role in development of ADHD and symptoms of impulsive and inattentive behavior. Bad parenting though can lead to antisocial conduct.

Taylor E.
Institute of Psychiatry, Kings College, London, UK

Recent research on the disorders of attention and activity has indicated inherited variants of genes controlling aspects of neurotransmission, abnormalities of structure and function in regions of frontal lobes and basal ganglia, failures to suppress inappropriate responses, and a cascade of failures in various kinds of cognitive performance and organization of behavior.

This review integrates the neurodevelopmental findings with findings from developmental psychopathology. It outlines several developmental tracks by which constitutional factors interact with the psychological environment.

In one set of tracks, altered brain states lead to cognitive alteration. An understimulating environment is evoked by (and may be genetically associated with) an inattentive and cognitively impulsive style during early childhood.

In another track, impulsive and inattentive behavior shows direct continuity through childhood into late adolescence.

In yet another track, impulsiveness evokes (and may be genetically associated with) critical expressed emotion from parents and inefficient coping strategies, which in turn contribute to the development of antisocial conduct.

This formulation emphasizes the need for several types of research: the mapping of biological findings onto different components of disorder, the combination of genetically informative designs with direct measurement of relevant aspects of the environment, and the use of longitudinal studies to examine predictive and mediating factors separately for different aspects of outcome.

Source: Development and Psychopathology (1999), 11: 607-628 Cambridge University Press doi:10.1017/S0954579499002230