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AACAP [American Academy of Child and Adolescent Psychiatry]

These practice parameters describe the assessment and treatment of early-onset bipolar disorder based on scientific evidence regarding diagnosis and effective treatment and on the current state of clinical practice.

Given the paucity of research on bipolar disorder in children and adolescents, many of the treatment recommendations are drawn from the adult literature.

Treatment involves the combination of pharmacotherapy and adjunctive psychosocial interventions. Antimanic agents (primarily lithium or valproic acid) are the mainstays of pharmacotherapy.

The treatment focuses on:
1. amelioration of acute symptoms;
2. the prevention of relapse;
3. the reduction of long-term morbidity; and
4. the promotion of long-term growth and development.

These parameters were approved by Council of the American Academy of Child and Adolescent Psychiatry on June 5, 1996.

Anonymous: AACAP official action. Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry, 1997 Jan, 36:1, 138-57.


Alcoholism (1)

The analysis of patterns of co-occurrence and cotransmission of affective disorders and alcoholism in families may provide clues for understanding the excess comorbidity between these conditions in clinical settings and in the general population.

Excess comorbidity between affective disorders and alcoholism was observed in all groups of relatives. However, the sharing of familial aetiological components was not a major contributor to the excess comorbidity between affective disorders and alcoholism.

Unipolar depression and alcoholism segregated independently in families, whereas a modest correlation between familial components of alcoholism and bipolar disorder was observed.

Maier W & Merikangas K: Co-occurrence and contransmission of affective disorders and alcoholism in families. Br J Psychiatry Suppl, 1996 Jun, :30, 93-100.

Alcohol (2)

It has been found that > 60% of bipolar I and almost 50% of bipolar II patients have a history of substance abuse (Regier et al., 1990).

Given the high prevalence of substance abuse in bipolar patients, it would be useful to determine more about the effect of substance abuse on demographic and clinical features and on the course of illness.

Preliminary results show differences in demographics, clinical features and course of illness between patient groups. These differences may illustrate the clinical effects of substance abuse on the course of bipolar disorder. Our results also indicate that there are differences between patients whose bipolar disorder began prior to and those whose disorder began after the onset of substance abuse.

Feinman JA & Dunner DL: The effect of alcohol and substance abuse on the course of bipolar affective disorder. J Affect Disord, 1996 Feb 12, 37:1, 43-9.

Children & Adolescents

Children and adolescents

To demonstrate the diagnostic and treatment challenges in juvenile-onset bipolar disorder.

There is evidence for the prophylactic antimanic effect of lithium carbonate in children and adolescents, but its specificity as an antimanic agent is still uncertain.

While the existence of juvenile-onset bipolar disorder is no longer in dispute, several outstanding issues related to diagnosis and long-term management remain. Careful prospective research will be necessary to sort out these issues definitively.

Steele M; Fisman S: Bipolar disorder in children and adolescents: current challenges. Can J Psychiatry, 1997 Aug, 42:6, 632-6.



This study examined choline bitartrate augmentation of lithium for rapid-cycling bipolar disorder.

Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds.

A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.

Stoll AL et al., Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry, 1996 Sep 1, 40:5, 382-8.

Diurnal variation

Assessed diurnal variation in the direction of mood switches in a sample of outpatients with rapid-cycling bipolar disorder who were on stable medication regimens. We predicted that patients would be more likely to switch from depression into mania or hypomania during the daytime hours and from mania/hypomania into depression overnight.

As predicted, switches that occurred between the morning and evening ratings were more likely to be from depression into mania/ hypomania or euthymia (64.3%) than in the opposite direction (35.6%). Similarly, switches that occurred between the evening rating and the next morning's ratings were more likely to be from mania/hypomania or euthymia into depression (64.8%) than in the opposite direction (35.2%).

Extended wakefulness, exposure to light, increased activity, and/or endogenous rhythms could contribute to the elevation of mood during the course of the day. Sleep, darkness, reduced activity, and/or endogenous rhythms could contribute to the tendency to switch into depression overnight.

Clinicians should attend to the time of day that clinical assessments are performed in patients with rapid-cycling bipolar disorder. Potential therapeutic implications include the use of light or activity during depression and use of induced sleep or exposure to darkness during mania/hypomania.

Feldman-Naim S et al., Diurnal variation in the direction of mood switches in patients with rapid-cycling bipolar disorder. J Clin Psychiatry, 1997 Feb, 58:2, 79-84.



Developed an adjunctive psychosocial intervention for patients with bipolar 1 disorder. Central to this intervention is the establishment of regularity in daily routines.

Compared this new treatment, interpersonal and social rhythm therapy (IPSRT), with a conventional medication clinic approach.

IPSRT is capable of influencing lifestyle regularity in patients with bipolar 1 disorder, with the possible benefit of protection against future affective episodes.

Frank E et al., Inducing lifestyle regularity in recovering bipolar disorder patients: results from the maintenance therapies in bipolar disorder protocol. Biol Psychiatry, 1997 Jun 15, 41:12, 1165-73.


Compared the effect of two different serum lithium levels on the psychosocial functioning of patients with bipolar I disorder.

Relapse was associated with large negative effects on psychosocial functioning. Patients in higher socioeconomic brackets had better psychosocial functioning than did those in lower brackets.

Patients receiving lithium doses that achieved standard serum levels had better psychosocial functioning than those receiving doses that achieved low serum levels; this effect was partially but not wholly mediated through relapse prevention.

For patients with bipolar I disorder, standard serum lithium levels may enhance psychosocial functioning, above and beyond the effects of relapse prevention.

Solomon DA et al., Serum lithium levels and psychosocial function in patients with bipolar I disorder. Am J Psychiatry, 1996 Oct, 153:10, 1301-7.

Melatonin therapy

Melatonin (1)

Lithium, carbamazepine, and valproic acid were ineffective or caused intolerable side effects. A trial of melatonin led to rapid relief of insomnia and aborted a manic episode. He has continued to take melatonin and adjunctive alprazolam for 15 months without recurrence of insomnia or mania. Affective disorders involving circadian dysregulation may respond to interventions that restore a normal sleep-wake cycle.

Robertson JM & Tanguay PE: Case study: the use of melatonin in a boy with refractory bipolar disorder. J Am Acad Child Adolesc Psychiatry, 1997 Jun, 36:6, 822-5.


A number of researchers have suggested that the phase (timing) of circadian rhythms in depressed patients is abnormal.

In normal volunteers, the concentration of salivary melatonin measurements has been shown to be significantly correlated with those obtained in plasma.

Measured plasma and salivary melatonin simultaneously in a sample of 12 medicated patients with rapid cycling bipolar disorder. The intraclass correlation coefficient between plasma and salivary measures of the dim light melatonin onset (DLMO) was 0.93.

Therefore salivary melatonin can be used to determine the time of the DLMO in this population.

Leibenluft E et al., Salivary and plasma measures of dim light melatonin onset (DLMO) in patients with rapid cycling bipolar disorder. Biol Psychiatry, 1996 Oct 15, 40:8, 731-5.

Life events

Negative life events

Examined the impact of severe negative life events on time to recovery from episodes of bipolar disorder. Although negative life events have been shown to influence relapse in bipolar disorder, research has not focused on life events and recovery.

Individuals with severe negative life events took more than 3 times as long to achieve recovery as those without severe life events, and the impact of life events was not mediated by medication compliance.

These results reveal that the psychosocial environment may play a much larger role in the course of bipolar disorder than previous biological models have suggested.

Johnson SL & Miller I: Negative life events and time to recovery from episodes of bipolar disorder. J Abnorm Psychol, 1997 Aug, 106:3, 449-57.


Neurobiological studies indicate a dysregulation of the dopaminergic and GABAergic neurotransmission in bipolar disorder.

Examined two large families segregating bipolar disorder, for linkage with the genes encoding dopamine beta-hydroxylase, the dopamine transporter DAT1, the dopamine D2, D3 and D5 receptors, and the alpha-1, alpha-5 and beta-1 subunits of the GABAA receptor.

Further analyses at these loci are warranted.

De bruyn A et al., A linkage study between bipolar disorder and genes involved in dopaminergic and GABAergic neurotransmission. Psychiatr Genet, 1996 Summer, 6:2, 67-73.


Abnormalities in the cellular phosphatidylinositol (PI) pathway have been proposed to be implicated in the pathophysiology of bipolar disorder. A platelet model was used to study phosphatidylinositol-4,5-bisphosphate (PIP2)

The relative percentage of PIP2 in the platelet membranes increased with cycling from the euthymic into the manic state. After lithium treatment, PIP2 decreased, and was similar to the euthymic state.

Soares JC et al., Platelet membrane phosphatidylinositol-4,5-bisphosphate alterations in bipolar disorder--evidence from a single case study. Psychiatry Res, 1997 Mar 24, 69:2-3, 197-202.

Sleep & mood


REM sleep and dreaming may play a crucial role in the processing of affect.

During this trial, subjects reported their dreams and rated their mood each morning. They also had their sleep recorded intermittently using the Nightcap, a compact computerized home sleep monitoring device.

We found that:
1. REM latency tends to increase as the mood improves in bipolars but is stable (and even decreases with mood improvements) in unipolar depressives;
2. dream content continues to systematically relate to prevailing mood state, but the patterns seen are different in unipolars and bipolars;
3. dreams of death are frequent in bipolar disorder and mark the transition of a mood shift upward.

Beauchemin KM & Hays P: Dreaming away depression: the role of REM sleep and dreaming in affective disorders. J Affect Disord, 1996 Nov 25, 41:2, 125-33.

Sleep & mood

Examined the effect of prior sleep (sleep duration, time of sleep onset, and time of wake onset) on the probability of being in a depressed, manic, or hypomanic episode on one or more subsequent days.

Of the three sleep parameters, decreased sleep duration was the best predictor of mania or hypomania the next day, followed by wake onset time. The association between sleep duration and subsequent mood was less consistent for depression than for mania or hypomania. Four of the patients showed no relationship between mood and any of the sleep variables measured.

These results reinforce the importance of monitoring, and perhaps controlling, sleep duration and wake onset time in at least some patients with rapid-cycling bipolar disorder.

Leibenluft E et al., Relationship between sleep and mood in patients with rapid-cycling bipolar disorder. Psychiatry Res, 1996 Jul 31, 63:2-3, 161-8.


Thyroid hormones

Hormones of the thyroid axis have been used to treat patients with any of several mental illnesses. However, in recent decades interest has focused almost exclusively on depression, though thyroid hormones, mainly thyroxine (T4), are used with lithium in rapid cycling bipolar disorder, a condition in which depression and mania rapidly alternate.

It seems likely that a tendency toward hypothyroidism can predispose to depression, but when depression occurs in a euthyroid patient, the thyroid axis is often invoked in the process of restitution.

Prange AJ Jr: Novel uses of thyroid hormones in patients with affective disorders. Thyroid, 1996 Oct, 6:5, 537-43.


Biological treatment

Rapid-cycling bipolar disorder (RCBD) is currently defined as the presence of at least four affective episodes per year. RCBD is often difficult to treat with standard therapies, thus dictating special treatment strategies. This is especially true for the treatment of RCBD with lithium, which has been described as insufficient to prevent the high-frequency episodes in up to 82% of cases.

There are several other possibilities for the biological treatment of RCBD, including:
the mood-stabilizers carbamazepine (CBZ) and valproate, neuroleptics, antidepressants, calcium channel blockers, l-thyroxine, benzodiazepines.
total sleep deprivation.

The utility of these agents and treatment procedures in the acute and prophylactic treatment of RCBD is reviewed.

Kr?ger S et al., Biological treatment of rapid-cycling bipolar disorder. Pharmacopsychiatry, 1996 Sep, 29:5, 167-75.

HR Therapy

Hormone replacement therapy

Report a case of mania occurring in a woman in late life who had begun receiving hormone replacement therapy for osteoporosis. They discuss related literature reports of mania or rapid cycling after adjunctive estrogen administration for refractory depression.

Young RC et al., Hormone replacement therapy and late-life mania [see comments]. Am J Geriatr Psychiatry, 1997 Spring, 5:2, 179-81.

Omega Fatty Acids

Omega-3 Fatty Acids

Many individuals with bipolar disorder, also called manic-depressive illness, do not respond to or do not tolerate the treatment options currently available (lithium, valproic acid, or carbamazepine).

Hence, new treatments with increased efficacy and lower toxicity are needed. Omega-3 fatty Acids are natural substances found in fish, which may produce some beneficial effects on mood. The purpose of this study is to evaluate the efficacy of omega-3 polyunsaturated fatty acids in patients with bipolar mood disorder.

Consenting subjects will receive capsules of either omega-3 fatty acids or placebo (olive oil) in addition to their current medication(s).

Marangell,LB: Omega-3 Fatty Acids in Bipolar Disorder: Stabilization Through Suppression of Second-Messenger Activity. Pilot study, unpublished.


Outcome studies of bipolar disorder, the majority of which were conducted before the use of lithium, divalproex, and carbamazepine, generally found that only 50 to 60% of patients achieved good recovery 6 to 12 months after a manic episode.

Over the past decade, a number of new pharmacologic studies have provided further information regarding the acute and long-term outcome of patients with bipolar disorder treated with these medications. In addition, better operational criteria to define outcome have been advanced, allowing for easier extrapolation of the results of clinical trials to clinical practice.

Reviewed the outcome of studies of lithium, divalproex, and carbamazepine in the acute treatment of episodes of mania and bipolar depression and in the maintenance treatment of bipolar disorder and their implications to clinical practice.

Keck PE Jr & McElroy SL: Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol, 1996 Apr, 16:2 Suppl 1, 15S-23S.


Birth seasonality

More than 40 studies have been done on seasonal birth patterns for schizophrenia, but only two small studies have been done for DSM-III-R bipolar disorder and none for schizoaffective disorder.

'Process' schizophrenia, paranoid schizophrenia, schizoaffective disorder and bipolar disorder all had statistically significant seasonal excess births from December through March. The largest excess was 5.8% for bipolar disorder. Major depression had significant excess births from March through May.

This study demonstrates that DSM-III-R bipolar disorder and schizoaffective disorder both have an excess of winter births, similar to that found in schizophrenia. Time series analysis, however, suggests that the causes may not be identical. Major depression, by contrast, has an excess of spring births.

Torrey EF et al., Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths. Schizophr Res, 1996 Sep 18, 21:3, 141-9.

Seasonal variation (Finland)

In patients with bipolar disorder, admissions for manic and depressive episodes frequently display a seasonal pattern.

There was no seasonal variation among all hospital admissions for bipolar disorder or schizophrenia. However, the first admission for a depressive compared with a manic episode of bipolar disorder occurred significantly more often in the autumn (33% v. 21% respectively). The peak difference occurred during the week after the autumnal equinox in September.

Our findings suggest that there is no seasonal variation in bipolar disorder, although in some patients the clinical course might be influenced by the autumn, as far as the likelihood of a first admission for depression is concerned.

Partonen T & L”nnqvist J: Seasonal variation in bipolar disorder. Br J Psychiatry, 1996 Nov, 169:5, 641-6.


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