Personality Disorders Medication

Updated: Nov 22, 2021
  • Author: David Bienenfeld, MD; Chief Editor: David Bienenfeld, MD  more...
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Medication Summary

Medication is rarely necessary to treat personality disorders. Indeed, differentiating personality disorders from pure mood disorders is important because patients with mood disorders will benefit from medication, particularly selective serotonin reuptake inhibitors (SSRIs). Patients with personality disorders and manifesting comorbid mood disorder require close medical supervision in terms of initiation and following of medication therapy.

Medications are in no way curative for any personality disorder. They should be viewed as an adjunct to psychotherapy so that the patient may productively engage in psychotherapy.

The focus is on the treatment of symptom clusters such as cognitive-perceptual symptoms, affective dysregulation, and impulsive-behavioral dyscontrol. These symptoms may complicate almost all personality disorders to varying degrees, and all of them have been noted in borderline personality disorder. [18, 19, 20, 21, 22, 23]

The assumption is that neurotransmitter abnormalities that transcend the concepts of axis I and axis II disorders underlie these symptom clusters. The strongest evidence for the efficacy of pharmacologic treatment of personality disorders has been for borderline personality disorder, but even this is based on a fairly small database of studies.



Class Summary

Because of overdose risk, tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) are usually not prescribed for patients with personality disorders. The selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants are safe and reasonably effective. However, because the depression of most patients with personality disorders stems from their limited range of coping capacities, antidepressants are usually less effective than in patients with uncomplicated major depression.

Antidepressants are most often prescribed for a limited time in patients with serious depressive episodes lasting longer than a few weeks.

Sertraline (Zoloft)

This agent selectively inhibits presynaptic serotonin reuptake.

Paroxetine (Paxil, Pexeva)

Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. Also has weak effect on norepinephrine and dopamine neuronal reuptake.

Fluoxetine (Prozac)

Fluoxetine selectively inhibits presynaptic serotonin reuptake with minimal or no effect on the reuptake of norepinephrine or dopamine.

Escitalopram (Lexapro)

This agent is an SSRI and an S-enantiomer of citalopram that is used for the treatment of depression. Escitalopram enhances serotonin activity because of selective reuptake inhibition at the neuronal membrane. Its mechanism of action is thought to be the potentiation of serotonergic activity in the central nervous system (CNS) through the inhibition of CNS neuronal reuptake of serotonin. The onset of depression relief may occur after 1-2 weeks, which is faster than the relief obtained from other antidepressants.


An antagonist at the 5-HT2 receptor, nefazodone inhibits the reuptake of 5-HT. In addition, this agent has a negligible affinity for cholinergic and histaminergic receptors.

Mirtazapine (Remeron)

Mirtazapine increases the availability of serotonin and norepinephrine.



Class Summary

These agents are useful for stabilizing the affective extremes in patients with bipolar disorder, but they are less effective in doing so in patients with personality disorders. They have some demonstrated efficacy in suppressing impulsive and particularly aggressive behavior in patients with personality disorder.

Valproic acid, divalproex sodium (Depakote, Depakene, Depacon, Stavzor)

Valproic acid is the most widely used agent in its class. It is modestly effective and generally well tolerated. It is chemically unrelated to other drugs that treat seizure disorders. Although its mechanism of action is not established, its activity may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. It also may potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect.



Class Summary

Some personality disorders (especially borderline personality disorder) produce transient psychotic periods, while others (eg, schizotypal personality disorder) feature chronic idiosyncratic ideation of nearly psychotic proportions.

Response to antipsychotics in patients with a personality disorder is less dramatic than it is in true psychotic axis I disorders, but symptoms such as anxiety, hostility, and sensitivity to rejection may be reduced. Antipsychotics are typically used for a short time, while the symptoms are active.

The atypical antipsychotics have almost completely replaced the traditional neuroleptics because of their safety margin, but neurologic risks (including tardive dyskinesia and neuroleptic malignant syndrome) are never absent. Risperidone and olanzapine are described here; however, quetiapine and ziprasidone may also be used. No evidence indicates that any of these has superior efficacy, and each one may have advantages and disadvantages with regard to adverse effects.

Risperidone (Risperdal)

Risperidone binds to the dopamine D2 receptor with an affinity that is 20 times lower than it is for the 5-HT2 receptor. This agent improves negative symptoms of psychoses and reduces the incidence of extrapyramidal adverse effects.

Olanzapine (Zyprexa)

Olanzapine may inhibit the effects of serotonin, muscarine, and dopamine.

Quetiapine (Seroquel)

Quetiapine may act by antagonizing the effects of dopamine and serotonin. Its efficacy is similar to that of risperidone and olanzapine. This agent causes fewer dose-dependent adverse effects and less concern regarding weight gain.