Take-home points

Patients with a mixture of MDD and personality disorder symptoms should have psychotherapy, ideally as maladaptive personality traits and defenses likely lead to increased stress and interpersonal difficulty; all of which are known to trigger recurrent MDEs

When possible, this should consist of evidence-based psychotherapies

Patients’ personality traits are often reciprocally exacerbated by MDD, and adequate treatment of the depression may lower the impact of their personality traits on their psychosocial functioning and improve functional outcomes, social wellbeing, and support

Rational polypharmacy techniques may be applied to treating psychiatric disorders such as MDD, but may also be applied to individual psychiatric symptoms, such as insomnia, as seen in Patient #2

• – In this case, hypnotic agents of differing mechanisms were added to ultimately achieve better sleep

  • GABAergic, antihistaminergic, and melatonergic agents were combined safely and successfully in a stepwise manner

Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – The evidence base for the effectiveness of both medication management and for eclectic, supportive psychotherapy in the treatment of personality disorder is quite limited

• – Prior to rational polypharmacy, attempts should have been made to find a formal, evidence-based psychotherapy practitioner for each patient

• – Both patients had pre-existing metabolic disorder symptoms

• – Despite close medical monitoring, choosing an SNRI with blood pressure issues and an atypical antipsychotic with greater weight-gain and blood glucose elevation issues was problematic

• – One patient developed a dystonia on a typical antipsychotic

• – This approach was chosen based on clinical experience with similar patients who were imminently escalating toward violence

• – This approach also was influenced by a pivotal single research study that examined a different patient population, schizophrenia

• – Use of an atypical antipsychotic approved for agitation management may have avoided the EPS

Possible action items for improvement in practice

• – Be aware that psychotropic drugs with noradrenergic potential are pressor agents and may allow for subtle increases in blood pressure, which may be problematic in treatment-resistant hypertensives

• – SNRIs, NDRIs, some TCAs, and some atypical antipsychotics possess NRI properties as well

• – Be aware that there are certain atypical antipsychotics that are more metabolically detrimental compared with those that are a bit more benign

• – Choose metabolically safer agents in those patients who are

  • Already suffering from metabolic illness

  • Have a clear family history and carry genetic risks for developing metabolic illness

Tips and pearls

Choosing an antipsychotic should be based on several factors

• – First, using approved agents for approved conditions affords some confidence in outcome, as a sufficient evidence base of at least two randomized trials exists, which have been audited by regulatory authorities

• – Second, an antipsychotic may be chosen based on tolerability

  • Some are more EPS prone, metabolically prone, sedation prone, etc.

• – Third, an antipsychotic may be chosen based on its pharmacodynamic receptor profile

  • For example, some atypicals carry SRI, NRI, 5-HT1A receptor agonsim, 5-HT2A/5-HT2C/5-HT7 receptor antagonism, which may promote more antidepressant-like and procognitive effects in theory

  • Most of the older, typical antipsychotics do not have this theoretical potential

• – Fourth, is cost

  • In one of the patient’s in this case, the CATIE schizophrenia trial was popular at the time and there was much writing about using the older, less costly generics

  • Haloperidol, low dose, was used due to this and to its routine, accepted use in treating acute agitated behavior

  • Much of the data regarding atypical use for agitation was not available at the time

  • In this case, use of the cheaper generic was effective but did cause dystonia problems, which resulted in a dental emergency

  • Given this, the net cost to the public insurance he was covered by was likely increased by using the less expensive generic typical antipsychotic

Two-minute tutorial

What is rational polypharmacy for Cluster B traits?

As there are no FDA approvals for the treatment of personality disorder, clinicians must start with a framework in mind for approach and clinical application when prescribing

Soloff¹ proposes a dimensional approach where the prescriber must choose particular target symptoms to treat rather than the personality disorder as a whole. The clinician should focus on prescribing medications to lower cognitive-perceptual, affective, or impulsive behavioral symptoms

Others suggest an outcome-focused approach where prescribers should clearly delineate the purpose of a pharmacologic intervention for both the patient and the clinician, choose outcomes that are measurable and related to functional improvements, and foster an understanding of the underlying psychobiologic mechanisms that cause the personality symptoms

Meta-analyses based on randomized controlled trials suggest that typical and atypical antipsychotics have a moderate effect on improving cognitive and perceptual symptoms and even larger effects on lowering anger. The antidepressants have little effect on depression and impulsive behavior, but may lower anxiety. The mood stabilizers tend to have large effects on improving impulsive behavior dyscontrol, anger, and anxiety

Gunderson² suggests an algorithm that is easy to follow

• – If a patient is accurately diagnosed with BPDO, the clinician must further delineate what symptom clusters are the most important to treat pharmacologically. If the patient has mild symptoms and requests no medication management, then psychotherapy is the ongoing treatment of choice. If the patient requests medication management, then use of an SSRI is warranted, as they may be the safest and best-tolerated option, but may have some of the lowest effect sizes globally when treating BPDO

• – If a patient is exhibiting more severe symptoms and the patient or the clinician feels pharmacotherapy is warranted, then a decision must be made as to which symptom cluster is to be treated: affective, impulsive/anger driven, or cognitive/perceptual

• – For affective symptoms, mood stabilizers have the greatest effects, followed by antidepressants

• – For impulsive/anger-based symptoms, antipsychotics seem to fare better than mood stabilizers. Both are better than antidepressants

• – For cognitive/perceptual symptoms, the antipsychotics have the best effect sizes

Posttest self-assessment question and answer

Which of the following are approved for treating mood swings?

A. Fluoxetine (Prozac)

B. Lamotrigine (Lamictal)

C. Asenapine (Saphris)

D. Alprazolam (Xanax)

E. All of the above

F. None of the above

Answer: F

None of the above has been approved as treatment for mood swings or mood lability as an individual symptom, or as a treatment for mood lability due to personality disorder. All of these may help decrease affective dyscontrol symptoms in clinical practice. Interestingly, the most commonly used SSRIs may have the least data and lowest effectiveness. Rapid downward mood swings into dysphoria, euphoria, or agitation are sometimes helped in an off-label manner in personality-disordered patients with all of these agents. Smaller open-label and controlled trials do exist supporting the use of antidepressants and the atypicals to a greater degree to support psychotherapy-based symptom reduction in personality-disordered patients.

References

1.Gregory RJ, Chlebowski S, Kang D, et al. A controlled trial of psychodynamic psychotherapy for co-occurring borderline personality disorder and alcohol use disorder. Psychotherapy 2008; 45:28–41.

2.Goldman GA, Gregory RJ. Preliminary relationships between adherence and outcome in dynamic deconstructive psychotherapy. Psychotherapy 2009; 46:480–5.

3.Gregory RJ, Delucia-Deranja E, Mogle JA. Dynamic deconstructive psychotherapy versus optimized community care for borderline personality disorder co-occurring with alcohol use disorders: a 30-month follow-up. J Nerv Ment Dis 2010; 198:292–8.

4.Goldman GA, Gregory RJ. Relationships between techniques and outcomes in borderline personality disorder. Am J Psychother 2010; 64:359–71.

5.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Revised, 4th edn. Washington, DC: American Psychiatric Association Press, 2000.

6.Swartz MS, Stroup TS, McEvoy JP, et al. What CATIE found: results from the schizophrenia trial. Psychiatr Serv 2008; 59:500–6.

7.Hori A. Pharmacotherapy for personality disorders. Psychiatry Clin Neurosci 1998; 52:13–19.

8.Stoffers J, Völlm BA, Rücker G, et al. Pharmacological interventions for borderline personality disorder. Cochrane Database Syst Rev 2010; 16:CD005653.

9.Soloff PH. Psychopharmacology of borderline personality disorder. Psychiatric Clin North Am 2000; 23:169–92.

10.Gunderson JG. Handbook of Good Psychiatric Management for Borderline Personality Disorder, 1st edn. Arlington, VA: American Psychiatric Publishing, 2014.

11.Links PS, Boggild A, Sarin N. Psychopharmacology of personality disorders: review and emerging issues. Curr Psychiatry Rep 2001; 3:70–6.

12.Ingenhoven T, Lafay P, Rinne T, Passchier J, Duivenvoorden H. Effectiveness of pharmacotherapy for severe personality disorders: meta-analyses of randomized controlled trials. J Clin Psychiatry 2010; 71:14–25.

¹ See References.

² See References.

Patient file

The Case:

Anxiety, depression, or pre-bipolaring?

The Question:

When to decide if someone is truly becoming bipolar disordered

The Dilemma:

Antidepressant activation can be a side effect or a sentinel event

Pretest self-assessment question (answer at the end of the case)

If a manic spell is instigated by initiation of an antidepressant, which of the following is likely to happen?

A. The induced mania will be more severe

B. The induced mania will last longer

C. The induced mania will be less severe and shorter in duration

D. None of the above