Discontinuation of maintenance treatment in bipolar disorder: risks and implications.

Authors: Suppes T, Baldessarini RJ, Faedda GL, Tondo L, Tohen M.
Consolidated Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, Mass., USA.
Harv Rev Psychiatry 1993 Sep-Oct;1(3):131-44

Risk of recurrence following discontinuation of lithium treatment in bipolar disorder.

Authors: Suppes T, Baldessarini RJ, Faedda GL, Tohen M.
Department of Psychiatry, Harvard Medical School, Boston, Mass.
Arch Gen Psychiatry 1991 Dec;48(12):1082-8

A Mixed depressive syndrome

Authors: Koukopoulos A, Faedda G, Proietti R, D'Amico S, de Pisa E, Simonetto C.
Lucio Bini Center, Rome, Italy
Encephale 1992 Jan;18 Spec No 1:19-21

The McLean First-Episode Psychosis Project: six-month recovery and recurrence outcome.

Authors:Tohen M, Stoll AL, Strakowski SM, Faedda GL, Mayer PV, Goodwin DC, Kolbrener ML, Madigan AM.
McLean Hospital, Belmont, MA 02178.
Schizophr Bull 1992;18(2):273-82

Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania

Authors: SL McElroy, PE Keck Jr, HG Pope Jr, JI Hudson, GL Faedda and AC Swann
Department of Psychiatry, University of Cincinnati College of Medicine, OH 45267-0559.
Am J Psychiatry 1992; 149:1633-1644

Ultra-ultra rapid cycling bipolar disorder is associated with the low activity catecholamine-O-methyltransferase allele.

Authors: Papolos DF, Veit S, Faedda GL, Saito T, Lachman HM
Program of Behavioral Genetics, Albert Einstein College of Medicine/Montefiore Medical Center, NY 10461, USA.
Mol Psychiatry 1998 Jul; 3(4):346-9

Comorbidity in mania at first hospitalization

Authors: SM Strakowski, M Tohen, AL Stoll, GL Faedda and DC Goodwin
Psychotic Disorders Program, McLean Hospital, Boston, MA.
Am J Psychiatry 1992; 149:554-556

Bipolar spectrum disorders in patients diagnosed with velo-cardio- facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder?

Authors: DF Papolos, GL Faedda, S Veit, R Goldberg, B Morrow, R Kucherlapati and RJ Shprintzen
Department of Psychiatry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
Am J Psychiatry 1996; 153:1541-1547

The McLean-Harvard First-Episode Project: 6-Month Symptomatic and Functional Outcome in Affective and Nonaffective Psychosis

Authors: Mauricio Tohen, Stephen M. Strakowski, Carlos Zarate, Jr., John Hennen, Andrew L. Stoll, Trisha Suppes, Gianni L. Faedda, Bruce M. Cohen, Priscilla Gebre-Medhin, and Ross J. Baldessarini
Biol Psychiatry 2000;48:467-476

In an interview with Jane Cartwright, a Mood Disorder Support Group of New York (MDSG) Newsletter contributor,
Dr. Gianni Faedda discusses common causes of misdiagnosis of Bipolar Disorder.

The number of people suffering from manic depression who are misdiagnosed with depression is staggering, according to Gianni Faedda, M.D., who will speak to MDSG on the subject December 3rd, 2001.

Are you one of them? Have you been told you suffer from depression alone, but you don't seem to get better with antidepressants? Is your depression worse even though you're on antidepressants? Does your depression recur? Come listen to a renowned researcher and practicing psychiatrist describe bipolar symptoms many physicians miss and why.

One of the most fascinating aspects of MDI is the patients’ lack of awareness of the illness. The medical term for this ‘deficit’ is anosognosia (from the Greek, lack of awareness of one’s illness).

The inability to recognize that changes of mood and behavior are due to an illness is an obstacle to seeking or continuing treatment.

This blind spot is often the cause of confusion and anger among relatives and friends, as it appears to be willful denial of the obvious. In a letter to a patient, a relative wrote:

Controlling the intensity, the duration and the frequency of episodes of MDI usually requires the use of medications. However, psychotherapy can help the patient with MDI learn how to manage their illness.

Several areas of treatment are included in the broad category of psychotherapy:
• Development of insight and self-monitoring of behavior and mood are the most important task of psychotherapy.

The stabilization of a patient with MDI is a long and delicate process that requires close collaboration between the patient and his/her physician, therapist or possibly, the treatment team.

Factors affecting the treatments’ outcome include patients’:
- illness type and course;
- environment (external factors);
- psychological make-up (internal factors);
- response to specific treatments or interventions.

It is estimated that almost 20% of untreated patients with MDI commit suicide and 20-50% attempt suicide at least once.

For an excellent overview on Suicide see Tondo et al., and the WHO Resources for Teachers on Suicide

The risk of suicide is highest among patients suffering from Depression with Hypomania (BP-II), followed by Mania with Depression (BP-I) and Unipolar Depression.

Mixed States, Chronic or Rapid-Cycling forms seem to increase the risk of suicidal behavior. Forms of agitated depression and Mixed Depressive Syndromes can lead to suicidal gestures, especially when active alcohol or substance abuse increases impulsiveness and impairs judgment.

MDI causes disability during symptomatic and during symptom-free periods. In the past it was assumed that once the symptoms were controlled, the person would return to a premorbid or baseline level of functioning without much delay. Longitudinal studies of interepisodic functioning among patients with MDI revealed a very different reality.

In order to clarify the effect of MDI on various aspects of life, a distinction has been made between symptomatic versus functional recovery.

Family life is very commonly affected, leading to conflict with parents and siblings during childhood and adolescence with spouses (or partners) and children in adulthood.

Tumultuous romantic lives -- extreme and sudden passions, multiple divorces or affairs testify to the emotional instability of many people with MDI.

In children we often observe frequent changes of school, school failures or dropouts, as the emotional instability can interfere with adequate or consistent functioning in school. Among adults, the work history is chaotic with frequent moves from job to job due to the person quitting or being fired.

MDI is an illness where episodes and intervals alternate in cycles, sometimes with a regular pattern.

The cycle of MDI is made of episodes and intervals and they cannot be separated and studied apart, as they constitute the basic unity of this illness. The longitudinal (long-term) observation of MDI in each person can reveal patterns of recurrence, clarify the relationship of episodes to psychosocial or pharmacological or environmental stressors and guide short- and long-term treatment.

The best estimate to date of the cost to society of Bipolar Disorder comes from a study published by Wyatt and colleagues in 1995.

Of the total estimated cost of $45 billion in 1991, only $7 billion were direct costs. Almost $38 billion was the indirect cost of this illness due to the loss of productivity, suicide and caregivers’ loss of productivity. These figures are estimates based on a prevalence rate for BPD of 1.3%.

“The modes of mania are infinite in species, but one alone in genus…”
-Aretaeus

Several attempts were made at defining subtypes of MDI based on severity of symptoms, recurrence rate and phases of illness. For example, the most common forms have the following features:
 Mania alternating with severe to mild depression (MD or Md), also called Bipolar I.
 Depression alternating with mild Mania or Hypomania (Dm) also called Bipolar II.

“We must regard all alleged injuries as possible sparks for the discharge of individual attacks, but…the real cause of the malady must be sought in permanent internal changes, which at least very often, perhaps always, are innate.
…The attacks of manic-depressive insanity may be to an astonishing degree independent of external influences.”
-Kraepelin

Often environmental factors play a role in the onset of an episode of MDI. This is commonly found early in the course of MDI, less often after the illness has followed his course for many years.

MDI can occur with other psychiatric or medical illnesses. The co-occurrence of two or more diseases is called Comorbidity. The most common diagnoses associated with MDI are other psychiatric conditions including Substance Abuse/Dependence (40%) and Anxiety Disorders (40%). -Brady

Approximately 20% of patients diagnosed with BPD suffer from Obsessive Compulsive Disorder, another 20% from Panic Disorder.

One of the most consistent findings in people suffering from MDI is a history of MDI, mood disorders and/or substance abuse in blood relatives.

A first-degree relative (parent, sibling or child) of a patient with Mania has a risk of suffering from Mania 8-18 times greater than a normal control (someone without a family history of Mania).

If one parent has Mania, the risk for the offspring is 25%. This means that 1/4 of children are likely to be ill. If both parents have a history of Mania, the risk for the offspring raises to 50-75% (2-3/4 of children are likely to be ill).

The first symptoms of this illness are often recognized in childhood or adolescence but more classic presentations of MDI are most common in early adulthood. It is rare to observe the onset of MDI in late life unless earlier episodes went undiagnosed or a medical condition contributes to its onset. (McDonald)

In a study of age at onset in 211 patients with DSM IV Bipolar Disorder (BD), Bellivier et al. reported a distribution of cases consistent with different ages of onset. In this study, age of onset was defined as the age when DSM IV criteria were first met for either depression or mania. In 41.4% of the population studied, this occurred at 16.9 years.

“Temperament …refers to an individual’s emotional nature, including his susceptibility to emotional stimulation, his customary strength and speed of response, the quality of his prevailing mood, and all peculiarities of fluctuation and intensity in mood, these phenomena being regarded as dependent upon constitutional make-up, and therefore largely hereditary in nature.”
-GW Allport

Psychiatric Disorders
Adjustment disorders
Alcohol/substance abuse/dependence
Anxiety disorders
Eating disorders
Major Depression, Dysthymia
Schizophrenia and Schizophreniform disorders
Somatoform disorders
Neurologic disorders
Extrapyramidal diseases (e.g., Parkinson's, Huntington's, Progressive Supranuclear Palsy)
Dementia (Alzheimer's, Pick’s, vascular)
Cerebral neoplasms
Cerebral trauma

Substance abuse:
Cocaine
Amphetamine
Hallucinogens
Caffeine
Over-the-counter diet pills (i.e. phenylpropanolamine)
Drug withdrawal states:
Alcohol
Antidepressants
Medications:
Steroids
Ritalin
Disulfiram (Antabuse)
Isoniazid
Sympathomimetic agents
Dopaminergic agents: L dopa, Bromocriptine
Infections:
Encephalitis
Neurosyphylis
AIDS
Endocrine:
Hyperthyroidism
Addison’s Disease

MDI has so many different presentations that a high rate of missed diagnosis and wrong diagnosis is not surprising. Several factors account for the high rate of misdiagnosis in MDI. These include:
 Hypomania is difficult to diagnose clinically.
 Patients are not reliable historians regarding manic/hypomanic symptoms.
 Short-term follow-up precludes observation of manic/hypomanic phases.

The presence of psychotic features in the course of MDI is a well-known phenomenon. Psychotic symptoms like delusions, hallucinations or catatonia/disorganized behavior can occur during episodes of Mania, Depression and Mixed States. If psychotic symptoms persist for two weeks or more after the resolution of mood symptoms, a diagnosis of Schizoaffective disorder is made.

Psychotic symptoms might be more common in those forms with an earlier age of onset.

From the Greek ‘alternating mood’, the term Cyclothymia was first used in psychiatry by E. Hecker in 1877 and was used by Emil Kraepelin as a synonym for the newly defined category of Manic-Depressive Insanity. Kraepelin described as subjects with a cyclothymic temperament ”…people who constantly oscillate hither and tither between the two opposite poles of mood, sometimes ’rejoicing to the skies, sometimes sad as death.”

C.F. Flemming first used Dysthymia (from the Greek abnormal mood) in psychiatry in 1844. In 1882 K.L Kahlbaum used the term Dysthymia to describe a predominantly depressive temperament that with Cyclothymia and Hyperthymia, belonged to subthreshold manifestation of Manic-Depressive Psychosis.

E. Kraepelin, in his conceptualization of Manic-Depressive Insanity preferred the term depressive temperament, a “…permanent gloomy emotional stress in all the experience of life.”