uestion: Does this patient with a treatment-resistant
depression meet DSM-IV criteria for one of the following personality
disorders?uestion: Does this patient with a treatment-resistant
depression meet DSM-IV criteria for one of the following personality
disorders?
Help: A study by Andrews et al¹ showed that the presence of personality disorder accounted for a significant amount of the variance in outcome of non-melancholic (as opposed to melancholic) depression. Fava et al found that fluoxetine seemed to work better when there was concomitant Cluster B personality disorder (Antisocial, Borderline, Histrionic).² In search of possible "specific" responses to medication in non-melancholic patients with personality disorder, the available options are considered for several personality disorders for which there is some information, as listed above. For none of these personality disorders is the available information so compelling that it would call for deviating from the standard algorithm for initial treatment. Rather, these considerations are raised here as the first step in thinking about the next set of options for a patient with an unsatisfactory response to initial treatment.
¹Andrews G, Neilson M, Hunt C, et al. Diagnosis, personality, and the long term outcome of depression. Br J Psychiatry 1990;157:13-18.
²Fava M, Bouffides E, Pava J, et al. Personality disorder comorbidity with major depression and response to fluoxetine treatment. Psychotherapy and Psychosomatics 1994;62:160-167.
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There is considerable overlap of the criteria for this personality disorder and social phobia, generalized type,¹ and depression with the Atypical Features Specifier. Both are conditions with relatively good prognosis for pharmacotherapy. These patients' depression is usually secondary to their unhappiness due to the severe restrictions their symptoms impose on their lives.² They may be extremely over-reactive to criticism, overly embarassed in front of others, and avoidant of important social interactions. The medications thought most useful are SSRI's and MAOI's.² If the full range of options in these classes has not been tried so far, it may be worthwhile to do so. Other medications with evidence of usefulness include benzodiazepines (clonazepam and alprazolam) and bupropion. Tricyclics do not seem to be particularly helpful.
Alcoholism is a common comorbid problem in this condition and if present may modify the allowable general approach.³
¹Schneier FR, Spitzer RL, Gibbon M, et al. The relationship of social phobia subtypes and avoidant personality disorder. Comp Psychiatry 1991;32(6):496-502.
²Rosenbaum JF, Pollock RA. The psychopharmacology of social phobia and comorbid disorders. Bull Menninger Clin 1994;58[2,Suppl. A]:A67-A83.
³Marshall JR. The diagnosis and treatment of social phobia and alcohol abuse. Bull Menninger Clin 1994;58[2,Suppl. A]:A58-A66.
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The depression in patients with borderline personality disorder appears to be of a distinct quality with particularly prominent symptoms of emptiness and anger.¹ SSRI's are established as effective for many patients for these symptoms, whereas tricyclics are not particularly useful and may worsen symptoms at times, and MAOI's may be occasionally useful. The prognosis for response from further pharmacotherapy trials after failure of the initial pharmacotherapy of this algorithm is probably guarded. Neuroleptics in low doses (eg haloperidol up to 6 mg per day, which is really not that low a dose for a neuroleptic-naive patient) were not efficacious in a controlled study with outpatients.² However, for the patient with very severe symptoms seen in the emergency or inpatient setting, neuroleptics do seem to calm the patient by blunting the hostile belligerence, suspiciousness, and motor excitement of some borderline patients and so their short term use is reasonable. This may be due to non-specific "tranquilizer" effects as well as to dopamine blockade.
The newer antipsychotics have come into predominant use because they have fewer side effects than standard, typical neuroleptics like haloperidol. There is one controlled study with olanzapine:³ in 19 female patients, more benefit were seen with olanzapine compared with placebo in all 4 core areas of psychopathology. Only 20% of patients had ever been hospitalized, so this was an outpatient group generally. Most patients did not complete the study, especially the placebo patients (1 of 9). The study was for 6 months, and dose averaged about 5 mg per day. There is also an open label study with olanzapine(4) at average dose of 7.5 mg found (in 11 patients) significant improvement from baseline in all domains measured. It appears from these two studies that results with the atypicals will be comparable to the typicals.
There is one controlled study with risperidone, but it is unpublished and only preliminary data was reported in a poster: risperidone was compared with placebo in 27 patients, at an average dose of 2.5 mg. There was no separation from placebo so far but there were trends for improvement in paranoia, psychoticism, interpersonal sensitivity, and phobic anxiety.(5)
Other options worth consideration(6) include lithium (if there are cyclothymic mood swings), venlafaxine (7), and carbamazepine or valproate (for problems with impulse control, although the depression may not particularly respond)(8). Naltrexone was helpful for dissociative symptoms in 6 of 9 borderlines, especially flashbacks, at doses of 25 to 100 mg qid [!].(9) Several earlier reports found a suggestion for naltrexone efficacy on self-injurious behaviour (at 50 mg per day, typically).(5)
At least three papers describe clozapine as an option for patients with severe, chronic symptoms. In two, the patients had psychotic-like features, and had failed on most other treatments, and the dose was 253 and 421 mg per day, i.e. full doses.(10) In another study in non-psychotic borderlines, the dose was 44 mg per day.while (11)
¹Rogers JH et al. Aspects of depression associated with borderline personality disorder. Am J Psychiatry 1995;152:268-270
²Soloff PH, Cornelius J, George A, et al. Efficacy of phenelzine and haloperidol in borderline personality disorder. Arch Gen Psychiatry 1993:50:377-385.
³Zanarini MC, Frankenburg FR. Olanzapine treatment of female borderline personality disorder patients: a double-blind, placebo-controlled pilot study. J Clin Psychiatry 2001;62:849-854.
(4)Schulz SC et al.Olanzapine safety and efficacy in patients with BPD and comorbid dysthymia. Biol Psychiatry 1999;46:1429-1435
(5)See discussion in: American Psychiatric Association. Practice Guideline for the Treatment of Patients wityh Borderline Personality Disorder. American Journal of Psychiatry 2001;158 October Supplement:1-52. Reference is: Schultz SC et al. Risperidone for BPO: a double blind study, in Proceedings of the 39th Annual Meeting of the American College of Neuropsychopharmacology. Nashville, Tenn, ACNP, 1999
(6)Soloff PH. Pharmacological therapies in borderline personality disorder. In: Paris J, Ed. Borderline Personality Disorder: Etiology and Treatment. American Psychiatric Press. Washington, D.C. 1993:319-347.
(7)Markovitz PJ, Wagner SC. Venlafaxine in the treatment of borderline personality disorder. Psychopharmacology Bull 1995;31(4):773-777.
(8)Wilcox JA. Divalproex sodium as a treatment for borderline personallity disorder. Ann Clin Psychiatry 1995;7(1):33-37.
(9) Bohus MJ et al. Naltrexone in the treatment of dissociative symptoms in patients with borderline personality disorder: an open-label trial. J Clin Psychiatry 1999;60:598-603.
(10)Frankenburg FR, Zanarini MC. Clozapine in patients with borderline personality disorder: a preliminary study. Comp Psychiatry 1993;34(6):402-405; Chengappa KNR et al. Clozapine reduces severe self-mutilation and aggression in psychotic patients with borderline personality disorder. J Clin Psychiatry 1999;60:477-484
(11)Benedetti F et al. Low-dose clozapine in acute and continuation treatment of severe borderline personality disorder. J Clin Psychiatry 1998;59(3):103-107.
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There has been increased awareness of and interest in this personality disorder since Kohut proposed the usefulness of specific new techniques of psychotherapy. Formal studies actually show a low rate of presence of narcissistic personality disorder in depressed patients, and a relatively higher rate in successfully remitted depressed patients.¹ However, Kohut² and an older literature describe a chronic dysthymia in narcissistic patients that reflects their pervasive lack of pleasure in life, lack of humor, lack of empathy for others, emptiness, hypochondriasis, but strong mood-responsiveness to admiration. Experience in clinical consultation reveals there are many such patients who fail adequate initial pharmacotherapy and that they are over-represented among persistently depressed, non-melancholic patients.³
A review of the literature reveals no clues as to whether continued sequential trials of medication will be helpful for such patients, but local experience is that they remain treatment-resistant to medication. One patient responded to bupropion. They do seem to gradually respond to long term psychotherapy if they remain committed to it.
Axis I comorbidity may point to some worthwhile pharmacotherapy options, however: press on "Continue..." below to review these options.
¹Ronningstam E. Pathological narcissism and narcissistic personality disorder in Axis I disorders. Harvard Rev Psychiatry 1996;3:326-340.
²Kohut H. The analysis of the self: a systematic approach to the psychoanalytic treatment of narcissistic personality disorders. New York: International Universities Press, 1971:16-17.
³Osser DN. A systematic approach to the classification and pharmacotherapy of non-psychotic major depression and dysthymia. J Clin Psychopharmacol 1993;13:133-144.
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Akiskal¹ cites a mixed "residual" group of personality disorders that comprised about two thirds of his group of lifelong intermittent dysthymic patients which were reported to be nonresponsive to tricyclics, MAOI's and lithium.² They had dependent features, and also histrionic and antisocial traits, hypochrondriasis, and also a family history of alcoholism. They frequently had problems with substance abuse themselves.
SSRI's were not available at the time of Akiskal's studies, and these trials were uncontrolled, so many of these patients would probably improve as they go through a number of adequate trials of pharmacotherapy as defined in this algorithm. However, if they have not responded satisfactorily and reach this point, their prognosis is assumed to be guarded for further sequential trials. Certainly emphasis should be placed on the psychosocial aspects of their overall treatment plan. They should be encouraged to invest fully in their psychotherapeutic work and not hold back in the hope that the next medication trial is likely to make all the difference.
Axis I comorbidity may point to some worthwhile pharmacotherapy options, however: press on "Continue..." below to review these options.
¹Akiskal HS. Dysthymic disorder: psychopathology of proposed chronic depressive subtypes. Am J Psychiatry 1983;140:11-20.
²Akiskal HS, Rosenthal TL, Haykal RF, et al. Characterological depressions: clinical and sleep EEG findings separating 'subaffective dysthymias' from 'character spectrum disorders.' Arch Gen Psychiatry 1980;37:777-783.
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There is little to be said about the depression pharmacotherapy implications of the other personality disorders. One paper was found suggesting that schizoid personality disorder was associated with worse four-month treatment outcome of depression with a tricyclic (maprotiline) compared to other personality disorder comorbidity.¹
Axis I comorbidity may point to some worthwhile pharmacotherapy options, however: press on "Continue..." below to review these options.
¹Sato T, Sakado K, Sate S. Is there any specific personality disorder or personality disorder cluster that worsens the short-term treatment outcome of major depression? Acta Psychiatr Scand 1993;88:342-349.
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