Do patients with borderline personality disorder belong to the bipolar spectrum?

BACKGROUND: This report examines clinical indicators for bipolarity in a cohort of patients suffering from Borderline Personality Disorder (BPD). METHODS: The study was conducted in the Cornell-Westchester Hospital, famed for its expertise in BPD. To avoid biasing our sample, we excluded all BPD patients who were active patients in our anxiety and mood disorders program. Through the use of both open clinical interviews and standardized diagnostic interviews (SCID), borderline patients were examined for evidence of bipolarity by five indicators: history of spontaneous mania, history of spontaneous hypomania, bipolar temperaments, pharmacologic response typical of bipolar disorder, and a positive bipolar family history. RESULTS: Depending on the level of bipolar disorder from the most rigorous (mania) to the most 'soft' (bipolar family history), between 13 and 81% of borderline patients showed signs of bipolarity. Based on what the emerging literature supports as rigorously defined bipolar spectrum (bipolar I and II), we submit that at least 44% of BPD belong to this spectrum; adding hypomanic switches during antidepressant pharmacotherapy, the rate of bipolarity in BPD reaches 69%. As expected from this formulation, most responded negatively to antidepressants (e.g. hostility and agitation) and positively to mood stabilizers. LIMITATIONS: Small sample size and retrospective gathering of data on treatment response. CONCLUSION: Patients with BPD more often than not exhibit clinically ascertainable evidence for bipolarity and may benefit from known treatments for Bipolar Spectrum Disorders. Large scale, systematic treatment studies with mood stabilizers are indicated.

Naturalistic experience with the use of divalproex sodium on an in-patient unit for adolescent psychiatric patients.

This paper focuses on the importance of data collected not only from controlled clinical trials, but also from naturalistic treatment experience. In particular we examine the use of divalproex sodium either as monotherapy or as part of combined therapy on an in-patient ward for adolescents aged 13-18 years. All admissions in which divalproex sodium use was attempted (n=36) were analysed over a 1-year period. The most common use was in patients with a mixed-presentation bipolar disorder (n=16), followed by patients with major depression (n=7), mania (n=4) or psychoses not otherwise specified (n=4). Divalproex sodium use was evaluated in the control of mania, psychosis, agitation, mood swings, aggression and/or anxiety. Overall, the use of divalproex sodium was associated with a marked improvement along all psychopathological variables in the vast majority of patients. Few side-effects or medical complications were noted. We believe that divalproex sodium is a potentially useful drug in adolescent patients with varying forms of psychopathology.

A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression.

We report results from a multicenter, placebo-controlled, randomized, double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in outpatients with major depression. Across five U.S. sites, 128 outpatients (mean age: 41.3 +/- 12.6; 63 men and 65 women) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994. All 128 patients completed a 1-week placebo washout period, and were then randomized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day (n = 55), fluoxetine up to 80 mg/day (n = 54), or placebo (n = 19). Subjects were evaluated weekly for the first 4 weeks, then at weeks 6, 9, and 12 with the 21-item HAMD and the Covi Anxiety Scale. There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity, as well as in the degree of depression and anxiety improvement. There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients. In summary, our results, although limited by the lack of a significant difference from placebo in treatment outcome, suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed outpatients, as well as similar safety and tolerability profiles.

The scientific, quasi-scientific and popular literature on the use of St. John's Wort in the treatment of depression.

St. John's Wort, also known as Hypericum, is an herbal product that is available in health food stores as an allegedly 'safe' alternative to antidepressants developed by the pharmaceutical industry. Recently it has received extensive coverage through the media, especially in the United States. To the best of our knowledge, Germany is the only country where it has been formally approved for clinical use. We reviewed both the vulgar and the scientific literature on this product. Although the few controlled studies that have been conducted pertain to adjustment disorder with depressed mood, several books and the media advocate its use for clinical and/or chronic depression. The high placebo rate in these studies, often in the 50% range, does indeed suggest that the controlled trials have been conducted on mild transient depressions; extrapolation to more serious or chronic depressions would therefore be unwarranted. We could not find any published literature comparing the efficacy of Hypericum to a standard antidepressant versus placebo. Furthermore, the studies claiming safety and freedom from potentially serious side effects appear flawed methodologically. Actually, little is known about the putative mechanism of action of Hypericum in depression; if indeed it does involve serotonergic mechanisms or monoamine-oxidase inhibition, it invites caution with concurrent use with an SSRI and, of course, with a MAOI. A skeptic might conclude that St. John's Wort should not be used until more definitive data are available. A less conservative view would be that, while its current widespread use is not warranted, the product may still have some merit for mild nonchronic depressive states below the clinical threshold. If this were conclusively proven, it would indeed constitute an important development in the field of antidepressants.

The effectiveness of the combination fluoxetine-naltrexone in bulimia nervosa.

Four patients with DSM-IV bulimia nervosa were treated in a crossover trial with naltrexone alone, fluoxetine alone, and a fluoxetine-naltrexone combination. Three patients presented a complete remission when treated with the fluoxetine-naltrexone combination.

Anxiety psychopathology predictive of outcome in patients with panic disorder and depression treated with imipramine, alprazolam and placebo.

This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week, placebo-controlled trial of alprazolam and imipramine (n = 126). Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment. Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4. At endpoint, the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance. This relationship was not evident for completers, suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced.

Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo.

Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment. The safety, side effects and patients' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study. Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation, fatigue/weakness, memory problems, ataxia and slurred speech. In the imipramine group blurred vision, tachycardia/palpitations, insomnia, sleep disturbance, excitement/nervousness, malaise, dizziness/faintness, headache, nausea/vomiting and decrease in appetite were worse than in the other groups. In the placebo group the anxious symptoms were most prominent. The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group. Strong predictors of side effects were not observed. If a side effect profile is known, it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance, safety and efficacy in each patient under treatment. Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients' quality of life.

The effect of valproate on bipolar spectrum temperamental disorders.

BACKGROUND: Cyclothymic or hyperthymic temperaments may belong to a bipolar spectrum of disorders. Patients with such temperaments, especially if there is a family history of bipolar disorder or an exacerbation of these conditions when exposed to tricyclic antidepressants, should be conceptualized as possessing variants of bipolar disorder. This conceptualization suggests that standard psychopharmacologic regimens used in treating bipolar disorder may be useful. In this report I examine the potential usefulness of valproate in treating temperamental variants of bipolar disorder. METHOD: The author reports his experience of treating patients with bipolar temperamental disorders in an Outpatient Affective Disorder Specialty Clinic. Three representative case reports are offered, as well as a discussion of the general issues in the diagnosis and treatment of these patients. RESULTS: In these cases, valproate not only treated the acute symptomatology that caused these patients to seek treatment, but also led to an amelioration of noxious life-long temperamental traits. These findings strengthen other research findings that suggest a link between bipolar disorder and limbic dysfunction and add to the validation of the concept of bipolar temperamental disorders. CONCLUSION: Valproate may be a safe and effective treatment for patients with cyclothymic and hyperthymic temperaments.

Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo.

This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode, Dysthymia, or Depressive Disorder NOS. The study's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam, imipramine and placebo on anxiety outcomes. A placebo-controlled, double-blind, parallel random assignment design was utilized over a total of 16 weeks. There was no medication effect on panic outcomes. At endpoint, percent of anticipatory anxiety (i.e., time spent worrying about having an anxiety attack) was significantly lower in the patients taking active medications vs. placebo. Phobic measures were significantly improved by alprazolam, vs. both imipramine and placebo early in the study; however, by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms. In addition, both active medications were significantly more effective than placebo in reducing depression. The same efficacy pattern (i.e., active medications superior to placebo) was observed on measures of general functioning. Importantly, there were no significant interactions observed between medication and presence of major depression on the depression measures, indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression. Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range, these results may not be transferrable to patients with panic disorder and severe major depression.

A three-generational presentation of separation anxiety in childhood with agoraphobia in adulthood.

School phobia belongs to a family of childhood anxiety states that appear to be related to adult forms of anxiety disorders, particularly to panic disorder with agoraphobia. School phobia appears to affect at least 5 percent of elementary school children and 2 percent of middle school children. Many of these children would be classified under the current DSM-III-R system of nomenclature as suffering from separation anxiety disorder. The present study is related to the elaboration of a three-generation family presentation of separation anxiety disorder manifesting itself as school phobia in childhood, which evolves toward panic disorder with agoraphobia in young adulthood and diffuse anxiety with hypochondriacal features in later life. All 13 genetically related members of the family investigated have been afflicted. The children with separation anxiety disorder and school phobia in this family who have been treated with imipramine have shown a resolution of anxiety symptoms that has allowed their successful return to school. The information from this family would fit into a model that describes a spectrum of anxiety disorders that present with different manifestations of overt psychopathology throughout the life cycle. We hope to follow this family prospectively over the next 30 years.

Center differences and cross-national invariance in help-seeking for panic disorder. A report from the cross-national collaborative panic study.

Help-seeking behaviour for treatment of panic disorder was investigated in the sample of the Cross-National Collaborative Panic Study Second Phase. A total of 1168 patients were entered into this trial in 14 countries. Although there were significant center differences in prior treatment and utilization of health services there were also similarities. Treatment had been provided mainly by general practitioners. Drug treatment consisted mostly of prescription of classical tranquilizers and had a longer duration than treatment by psychotherapy. Patients with agoraphobic avoidance, past major depression and longer duration of illness used medical and psychiatric treatment facilities more intensely. Older and more severely disabled subjects were more frequently treated by medical health care providers and were more likely to receive psychotropic drugs. The results indicate that general practitioners carry an important load in the treatment of panic disorders but may need more information about recent development in pharmacotherapy for this condition.

Effects of phototherapy on non-seasonal unipolar and bipolar depressive spectrum disorders.

In a group of 17 patients with non-SAD depressive disorders we compared the response of bipolar spectrum versus unipolar patients to treatment with light therapy. The main hypothesis was that bipolar spectrum depressed patients would preferentially respond to bright light therapy as compared to unipolar depressed patients. All patients were treated with either 400 or 2500 lux phototherapy for 2 h on seven consecutive days. All outcome measures, which included the SIGH-SAD, CGI, and the Anxiety and Depressive Factors of the SCL-90, showed significant improvement in the bipolar vs. the unipolar spectrum patients. Unexpected this occurred regardless of the intensity of the light. These changes were judged to be quite clinically significant. All patients showing response were noted to have maintained their response at a 3-month follow-up.

Patients with panic disorder unaccompanied by depression improve with alprazolam and imipramine treatment.

Patients with panic disorder (N = 1168) were enrolled in a multicenter, 8-week, double-blind clinical trial of imipramine, alprazolam, and placebo to analyze whether the effectiveness of these agents is dependent on the depressive/dysphoric symptomatology which often coexists in panic disorder patients. In addition to analyses performed on the whole sample of patients, the authors conducted analyses on a subsample (N = 312) defined by multiple criteria to ensure the absence of depression and dysphoria. In both the overall sample and the nondepressed subsample, the clinical response to imipramine or alprazolam was found to be independent of the presence of depression or dysphoria. In panic disorder patients for whom pharmacotherapy is being considered as treatment, the absence of depression is apparently not a contraindication.

The sequence of improvement of the symptoms encountered in patients with panic disorder.

Patients who meet DSM-III-R criteria for a diagnosis of panic disorder often show a complex mixture of psychopathological symptoms, including panic attacks (spontaneous and situational), anxiety (anticipatory and generalized), phobias (fear and avoidance), depression/dysphoria, and social and occupational disability. Various theories about the pathogenesis of these symptoms have been advanced that focus on a given symptom (e.g., panic, phobia) being primary in these disorders, with concurrent symptoms seen as epiphenomena or as secondary and reactive to a core symptom. This study, conducted on a large sample of panic disorder patients (N = 1,168), examines the temporal sequential pattern of symptom improvement in these patients, and explores how these relationships relate to various pathogenic theories. Our multiple analyses, when considered together, tend not to support any pathogenic theory that views a given symptom as being central to the overall disorder; our findings have obvious implications for theoreticians and clinicians interested in the study and treatment of panic and anxiety disorders.

The Panic-Associated Symptom Scale: measuring the severity of panic disorder.

The Panic-Associated Symptom Scale (PASS) is presented as a new measurement of the severity of the core symptoms of panic disorder. This first description addresses the rationale for its design and its scoring, score distributions, test-retest reliability, correlations within the PASS and with other scales, principal component structure, and response to drug therapy. Data are presented from a large study group of patients with panic disorder (n = 1168). Problems in measuring panic disorder are discussed.

Psychopharmacological treatment of avoidant personality disorder.

Avoidant personality disorder is quite prevalent and can result in marked impairment in social and occupational functioning. Since it has been conceptualized as a disorder of personality, only limited studies of its potential sensitivity to pharmacological treatments have been reported, usually in relation to the treatment of social phobia. This report examines the relationship of avoidant personality disorder to social phobia and describes the successful pharmacotherapy of several patients whose targeted outcomes were their avoidant traits. Our experience with resolution of avoidant features with treatment with monoamine oxidase inhibitors or fluoxitene recommends a 2- to 3-month trial of these agents in patients with avoidant personality disorder whether or not there is comorbidity for another DSM-III-R axis I disorder.

Discordance of self ratings versus observer ratings in the improvement of depression: role of locus of control and aggressive behavior.

Depression is mainly a subjective experience. Its severity is not always assessed in the same way by patients and clinicians. Divergences between self- and hetero-evaluation of depressive symptoms and severity are also dependent on the cognitive style of a patient. A high proportion of patients judged improved by their physicians continue to declare that serious symptoms are present. These patients tend to use a cognitive style that has been called external locus of control. Some investigators have correlated the locus of control in depressive patients with hostile traits, pointing out that the severity of symptomatology seems to be associated with some forms of hostility, with an external cognitive mode representing particular communications from patients to their caregiver. The present clinical study shows the influence of cognitive style and aggressive behavior on the discordance seen between self- and hetero-evaluation for depression during the improvement of depression.

High-affinity 3H-imipramine binding sites: a possible state-dependent marker for major depression.

Ten patients with DSM-III diagnoses of nonbipolar recurrent major depression were studied in an attempt to assess the relationship between 3H-imipramine binding site density and clinical depressive state. They were compared with eight healthy controls who had no past or family history of affective disorders. Evaluations with the Hamilton Rating Scale for Depression and the Self-Rated Scale for Depression were done on the same day as platelet collection at baseline, and also at 2 and 5 weeks after the beginning of treatment with tricyclic antidepressants. The number (Bmax) and the affinity (Kd) of platelet 3H-imipramine binding sites were highly correlated with the improvement of the clinical depression. These results raise the interesting possibility that a decrease in 3H-imipramine binding sites may be a state-dependent marker in patients suffering from nonbipolar recurrent major depression.