By, Ivan Goldberg, MD

AU – Soloff PH AU – Lis JA AU – Kelly T AU – Cornelius J AU – Ulrich R
TI – Risk factors for suicidal behavior in borderline personality disorder.
SO – American Journal of Psychiatry 1994 Sep;151(9):1316-23
AB – OBJECTIVE: This study identified potential risk factors for suicidal behavior in patients with borderline personality disorder defined by the Diagnostic Interview for Borderline Patients and by DSM-III-R criteria for patients who did and did not attempt suicide. METHOD: Histories of suicide attempts and attempt characteristics were obtained by Schedule for Affective Disorders and Schizophrenia interviews from 84 patients with borderline personality disorder and were related to severity of borderline pathology, diagnostic comorbidity, and state and trait symptoms. RESULTS: There were 61 patients with a lifetime history of suicide attempts (72.6%), with an average of 3.39 (SD = 2.87) attempts per patient. Attempters were significantly older than nonattempters, with more impulse actions, antisocial personality disorder comorbidity, and state depression. State depression was significantly less severe in patients who had attempted suicide in the present episode (or past year) than in patients who had attempted suicide only in the past. A comorbid diagnosis of major depression, alcoholism, or drug use disorder did not distinguish attempters from nonattempters. Suicide attempt in the present episode was best predicted by the number of prior lifetime attempts. A highly serious intent to commit suicide was predicted by the number of lifetime attempts and subjective depression, while a low intent was predicted by a mixed subtype of borderline personality disorder plus schizotypal personality disorder and paranoid ideation. A high degree of medical lethality was predicted by number of lifetime attempts, older age, and hysteroid dysphoria, while low lethality attempts were associated with high degrees of anger. CONCLUSIONS: Risk factors for suicidal behavior in patients with borderline personality disorder include older age, prior suicide attempts, antisocial personality, impulsive actions, and depressive moods but not comorbid affective disorder, alcoholism, or drug use disorders.

AU – Gitlin MJ
TI – Pharmacotherapy of personality disorders: conceptual framework and clinical strategies. [Review] SO – Journal of Clinical Psychopharmacology 1993 Oct;13(5):343- 53
AB – This article delineates the conceptual models used when medications are prescribed for patients with personality disorders and reviews the data on the efficacy of these medications. Studies before 1980 are difficult to interpret because of changes in diagnostic criteria. Nonetheless, early studies on non-DSM-III disorders such as pseudoneurotic schizophrenia, emotionally unstable character disorder, hysteroid dysphoria, and subaffective disorders indicated the potential utility of pharmacotherapy for treating personality disorders. Models to consider in evaluating the possible use of medications for treating personality disorders are: (1) treating the disorder itself; (2) treating symptom clusters within and across disorders; and (3) treating associated axis I disorders. Among the current personality disorders, borderline personality disorder has been the most extensively studied, with antipsychotic agents being the most well-documented treatment. Monoamine oxidase inhibitors, fluoxetine, and carbamazepine show promise. Schizotypal disorders may respond to low-dose antipsychotic drugs. Although heuristically valuable, the symptom cluster approach to treatment has not yet been validated. Axis I disorders, especially depression, are frequently associated with all personality disorders. Dependent personality disorder is linked to panic disorder with agoraphobia, whereas avoidant personality disorder is associated with social phobia and panic. In general, pharmacotherapy for axis I disorders is less effective in the presence of a comorbid personality disorder. Despite the modest benefits seen in many studies, pharmacotherapy can add significantly to the overall treatment of those with personality disorders. Future research must carefully assess the effect of comorbid axis I disorders on responses. The symptom cluster/psychobiologic dimension approach should be investigated in clinical studies. [References: 88]

AU – Soloff PH AU – Cornelius J AU – George A AU – Nathan S AU – Perel JM AU – Ulrich RF
TI – Efficacy of phenelzine and haloperidol in borderline personality disorder.
SO – Archives of General Psychiatry 1993 May;50(5):377-85
AB – OBJECTIVE: To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. PATIENTS: One hundred eight consecutively admitted borderline inpatients defined by Gunderson’s Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. INTERVENTIONS: Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. MAIN OUTCOME MEASURES: Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). RESULTS: Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. CONCLUSIONS: Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated.

AU – Moller SE
TI – Serotonin, carbohydrates, and atypical depression. [Review] SO – Pharmacology & Toxicology 1992;71 Suppl 1:61-71
AB – At least three categories of atypical depression have been described. The hysteroid dysphoria is characterized by repeated episodes of depressed mood in response to feeling rejected, and a craving for sweets and chocolate. Two other issues are characterized by a cyclical occurrence of changes of mood and appetite, i.e., the late luteal phase dysphoric disorder (DSM-III-R, appendix), or “the premenstrual syndrome” (PMS), and the major depression with seasonal pattern (DSM-III-R), or seasonal affective disorder (SAD). The reactive mood changes are frequently accompanied by features as hypersomnia, lethargy and increased appetite, particularly with a preference for carbohydrates. Central serotonin pathways participate in the regulation of mood and behavioural impulsivity, and modulate eating patterns qualitatively and quantitatively. Depressives with PMS og SAD benefit, in general, from treatments with serotonin potentiating drugs, suggesting that brain serotonin plays a role in the pathophysiology. Ingestion of carbohydrates increases the plasma ratio of tryptophan to other large neutral amino acids in man and animal, and the serotonin synthesis in the rat brain. Based on these findings it has been suggested that the excessive carbohydrate intake by patients with PMS and SAD reflects a self- medication that temporarily relieves the vegetative symptoms via an increased central serotonergic activity. [References: 74]

AU – Soloff PH AU – Cornelius J AU – George A
TI – The depressed borderline: one disorder or two?. [Review] SO – Psychopharmacology Bulletin 1991;27(1):23-30
AB – Depression in the borderline patient may present as a reactive mood state, an expression of character, or an independent comorbid affective disorder. The symptom picture is most often heterogeneous, “atypical,” and chronic. Pharmacologic trials with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) produce modest improvement on a variety of symptoms, though not always on depression. Medication effects on depressed mood in borderline personality disorder (BPD) are independent of comorbid diagnoses of major depression, atypical depression, or hysteroid dysphoria. Residual symptoms are the rule. A literature review, including studies of comorbidity, longitudinal followup, family history, and laboratory and pharmacotherapy studies, suggests that the borderline patient has both a core biologic affective dysregulation and a pathologic personality organization. The combination of constitutional and psychodynamic etiologies for borderline pathology requires consideration of both pharmacotherapy and psychotherapy in any comprehensive treatment. [References: 43]

AU – Larsen JK
TI – MAO inhibitors: pharmacodynamic aspects and clinical implications. [Review] SO – Acta Psychiatrica Scandinavica, Supplementum 1988;345:74- 80
AB – Many recent studies have stressed the importance of maintaining the MAO inhibitors in the therapeutic arsenal for depressive patients. In most cases MAO inhibitors are generally safe and as well tolerated as the cyclic antidepressants. It has been suggested that MAO inhibitors are more likely to benefit depressed patients with atypical vegetative symptoms like gain in weight, sleep or libido. However, they may be therapeutic for a wide spectrum of psychiatric disorders ranging from depression with generalized anxiety or phobia, hysteroid dysphoria and endogenous affective illness refractory to conventional therapies. Because of the hazards: drug-drug and drug-food interactions, the irreversible and unspecific MAO inhibitors are only to be recommended on the condition that a good patient compliance can be obtained. [References: 19]

AU – DePaulo JR Jr AU – Simpson SG TI – Therapeutic and genetic prospects of an atypical affective disorder [published erratum appears in J Clin Psychopharmacol 1988 Feb;8(1):13]. [Review] SO – Journal of Clinical Psychopharmacology 1987 Dec;7(6 Suppl):50S-54S AB – The utility of bipolar type II affective disorder subgrouping is discussed. There is low diagnostic agreement among clinicians for this putative condition. However, the clustering of cases in families and the poor response to standard treatments suggest that it is a distinct subgroup. The clinical features of the depressive phase of this condition including chronicity, intermittency, hyperphagia, hypersomnia, and reactivity relate it to the constructs of “hysteroid dysphoria,” atypical depression, and seasonal affective disorder. Its association to several abnormal motivated behaviors such as alcoholism and eating disorders allows the speculation that a distinct morbid mechanism involving serotonin may underlie it and that new serotonin reuptake blocking drugs may be useful in treating it. Finally, the genetic identity of this subgroup in all likelihood will be established or rejected by genetic linkage studies utilizing the restriction fragment length polymorphism map of the genome. [References: 42]

AU – Dowson JH
TI – MAO inhibitors in mental disease: their current status. [Review] SO – Journal of Neural Transmission. Supplementum 1987;23:121- 38
AB – Available MAOIs seem to be mainly indicated for the heterogeneous group of patients with depressive syndromes. Although groups of patients with all the recognized major subtypes of depression (including “endogenous depression”) probably respond in varying degrees, MAOIs appear to be particularly indicated for out- patients with “neurotic depression” complicated by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feeling rejected. MAOIs can also be effective in several anxiety syndromes, in particular panic disorder. Other reports have claimed success in a variety of other syndromes including bulimia, anorexia nervosa, obsessive-compulsive neurosis, atypical facial pain and some other types of chronic pain, childhood attention deficit disorder and delusions of infestation by parasites. The nature of any underlying personality disorder is an important response variable and the assessment of personality should be encouraged in further studies. The development of new drugs raises the prospect of a range of MAOIs targeted at specific patient populations. Tranylcypromine also merits further investigation as clinical experience suggests that it can produce a dramatic response in some patients with phenelzine-resistant disorders. This may be due, at least in part, to its amphetamine-like effects. [References: 75]

AU – Schuman M AU – Gitlin MJ AU – Fairbanks L
TI – Sweets, chocolate, and atypical depressive traits.
SO – Journal of Nervous & Mental Disease 1987 Aug;175(8):491- 5
AB – An original questionnaire, the Foods and Moods Inventory (FMI) was used to investigate appetite for sweets and chocolate and its relationship to dysphoric mood. The FMI was administered to a group of subjects with an identified interest in chocolate (chocolate group, N = 73), a comparison sample (comparison group, N = 172), and a sample of former alcoholics (N = 22). Those who reported “self-medicating” with sweets or chocolate were more likely to have personality traits associated with hysteroid dysphoria, an atypical depressive syndrome. In addition, the tendency to eat compulsively, in general, and appetite for sweets and chocolate, in particular, were significantly greater among women.

AU – Soloff PH AU – George A AU – Nathan RS AU – Schulz PM
TI – Characterizing depression in borderline patients.
SO – Journal of Clinical Psychiatry 1987 Apr;48(4):155-7
AB – The comorbidity of depression and borderline disorder was studied in 39 symptomatic borderline inpatients defined by the Diagnostic Interview for Borderlines using three independent methods for assessing depression and three definitions of depression. Evaluations were conducted by the Schedule for Affective Disorders and Schizophrenia interviews for Research Diagnostic Criteria (RDC) depressive disorders, by clinical ratings for atypical depressive disorder, and by self-rated questionnaires for hysteroid dysphoria. Diagnoses of an RDC depression were made in 25 (64.1%), atypical depressive disorder in 16 (41%), and hysteroid dysphoria in 25 (64.1%) of the borderline patients. Two depressive diagnoses were present in 64.1% of patients, while 17.9% of patients met criteria for all three depressive disorders. No one method accurately characterized depression in borderline patients.

AU – Kayser A AU – Robinson DS AU – Nies A AU – Howard D TI – Response to phenelzine among depressed patients with features of hysteroid dysphoria. SO – American Journal of Psychiatry 1985 Apr;142(4):486-8
AB – A 21-item questionnaire eliciting features of hysteroid dysphoria was administered to 51 depressed outpatients. Of the 47 patients who completed a 6-week double-blind study comparing the efficacy of amitriptyline and phenelzine, 14 had questionnaire scores greater than or equal to 13 (high score) and 33 had scores less than 13 (low score). Nine of nine high-score patients responded to phenelzine; only three of five high-score patients responded to amitriptyline. Low-score patients responded equally well to either drug (79% improved). These findings suggest that some depressed patients have features of hysteroid dysphoria and that these patients respond preferentially to phenelzine.

AU – Liebowitz MR
TI – Newer uses for older psychotropic medications. [Review] SO – Hospital & Community Psychiatry 1982 Apr;33(4):282-6
AB – New uses are still being discovered for a number of psychotropic agents that have been available for some time. Among the more important recent discoveries are the efficacy of the tricyclic antidepressants for panic disorder and agoraphobia with panic attacks; the use of the monoamine oxidase inhibitors for the above disorders and for atypical depression and hysteroid dysphoria; the use of propranolol for anxiety disorders and for uncontrollable violent outbursts; the antianxiety and antipanic effects of clonidine; and the usefulness of lithium in treating schizophrenia and schizoaffective disorder and for emotionally unstable character disorders. In addition to strengthening the therapeutic armamentarium, the author says, the discovery of new drug response patterns helps generate or strengthen hypotheses about the pathophysiology of various psychiatric disorders. [References: 47]

AU – Beeber AR AU – Kline MD AU – Pies RW AU – Manring JM Jr
TI – Hysteroid dysphoria in depressed inpatients.
SO – Journal of Clinical Psychiatry 1984 Apr;45(4):164-6
AB – Hysteroid dysphoria has been described in outpatient populations and is thought to be a subtype of atypical depression involving rejection sensitivity and therapeutic response to monoamine oxidase inhibitors. The presence of hysteroid dysphoria was assessed, using a semistructured interview, in 18 depressed inpatients. The 6 patients who met the criteria for hysteroid dysphoria did not differ from other depressed patients in severity, premorbid adjustment, number of atypical features, or presence of melancholia. Implications for treatment are discussed.

AU – Spitzer RL AU – Williams JB TI – Hysteroid dysphoria: an unsuccessful attempt to demonstrate its syndromal validity. SO – American Journal of Psychiatry 1982 Oct;139(10):1286-91
AB – Hysteroid dysphoria has been described as a chronic illness characterized by recurrent periods of depression precipitated by a specific type of stress and associated with a histrionic personality. In addition, there are specific atypical symptoms. The authors tested the syndromal validity of this proposed category in a sample of 1,324 patients with mild depression reported on by psychiatrists in a questionnaire survey. They found 41 (3.1%) who fit a pattern consisting of the basic features of the condition. However, patients who fit this pattern were not more likely to have substantially more atypical symptoms than patients without this pattern. The authors conclude that the syndromal validity of hysteroid dysphoria is not supported. AU – Stone MH TI – Depression in borderline adolescents. SO – American Journal of Psychotherapy 1981 Jul;35(3):383-99
AB – Etiologically, adolescents considered borderline by the criteria in common use are on a continuum between primarily biological and primary psychological disorders. Depression is common, and may be masked (in many cases of ulcer, anorexia, substance abuse, school avoidance) or overt (viz., early onset endogenous depression, hysteroid dysphoria, cases with severe deprivation). Illustrative cases are provided, along with recommendations for treatment.

AU – Stone MH
TI – Assessing vulnerability to schizophrenia or manic- depression in borderline states.
SO – Schizophrenia Bulletin 1979;5(1):105-10
AB – In a discussion of the article on genetic determinants of borderline conditions by Siever and Gunderson, a phenotypic continuum between pure schizotypal and pure affective conditions is postulated. Many “borderline” cases are seen as attenuated forms of schizophrenia, schizoaffective psychosis, or manic-depression. A Venn diagram illustrates differences among syndromes described by Gunderson, Kernberg, Spitzer, and Klein (“hysteroid dysphoria”). Evidence is presented suggesting that Gunderson’s borderline syndrome contains more schizotypal individuals than Kernberg’s, whereas hysteroid dysphoria is nearer the affective pole of the continuum. A second diagram illustrates how the strength and nature of the genetic factors vary according to the syndrome.