What is the best medication to use in a patient with mental illness where current treatment is inadequate?

From the Guidelines

The best approach for a patient with inadequate mental illness treatment is to evaluate their specific diagnosis, symptoms, and treatment history, and consider optimizing the current medication, adding an augmenting agent, or switching to a different medication class entirely, with clozapine being a viable option for schizophrenia with inadequate response, as recommended by the American Psychiatric Association 1. When current treatment is inadequate, a psychiatrist should assess the patient to determine the best course of action. For depression, options might include switching from an SSRI to an SNRI like venlafaxole (75-225 mg daily), adding an atypical antipsychotic like aripiprazole (2-15 mg daily) to an antidepressant, or trying a different mechanism like bupropion (150-450 mg daily). For schizophrenia with inadequate response, clozapine (starting at 12.5 mg and titrating up to 300-900 mg daily) is often considered, as it has been shown to be effective in reducing symptoms and improving treatment outcomes 1. Some key points to consider when managing schizophrenia include:

• Antipsychotic monotherapy should be strived for, with clozapine being a viable option for patients who have not responded to other treatments 1
• Medication adherence is crucial, and long-acting injectables or blood concentration measurements may be considered to affirm compliance and proper serum levels 1
• Antipsychotic polypharmacy may be appropriate for patients who still have symptoms despite treatment attempts with an adequate dose, an adequate choice of therapeutic, and confirmed adherence 1
• Pharmacogenetics may offer a fast and cost-effective method to determine better optimized treatment approaches in the future 1 It is essential to note that treatment changes should be made gradually, with close monitoring for side effects and therapeutic response, typically allowing 4-6 weeks to assess effectiveness, as recommended by the American Society of Clinical Oncology 1. Medication adjustments should always be accompanied by appropriate psychotherapy and lifestyle interventions for comprehensive treatment.

From the FDA Drug Label

It is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. The efficacy of oral olanzapine in the treatment of manic or mixed episodes was established in 2 short-term (one 3-week and one 4-week) placebo-controlled trials in adult patients who met the DSM-IV criteria for bipolar I disorder with manic or mixed episodes In one 6-week placebo-controlled combination trial, 175 outpatients on lithium or valproate therapy with inadequately controlled manic or mixed symptoms (Y-MRS ≥16) were randomized to receive either olanzapine or placebo, in combination with their original therapy Olanzapine (in a dose range of 5-20 mg/day, once daily, starting at 10 mg/day) combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L to 1. 2 mEq/L or 50 μg/mL to 125 μg/mL, respectively) was superior to lithium or valproate alone in the reduction of Y-MRS total score

The best medication to use in a patient with mental illness where current treatment is inadequate is olanzapine, as it has been shown to be effective in reducing symptoms of manic or mixed episodes in patients with bipolar I disorder.

• Key benefits of olanzapine include its ability to be used as monotherapy or in combination with lithium or valproate.
• Dosage ranges from 5-20 mg/day, once daily, starting at 10 mg/day.
• Clinical trials have demonstrated the efficacy of olanzapine in reducing Y-MRS total score in patients with inadequately controlled manic or mixed symptoms 2.

From the Research

Treatment Options for Mental Illness

When current treatment is inadequate, several medication options can be considered to manage behaviors in patients with mental illness.

• The combination of olanzapine and fluoxetine has been shown to be effective in treating bipolar depression 3 and psychotic major depressive disorder 4.
• Olanzapine alone has also been found to be effective in treating psychotic depression, with a response rate of 67% in one study 5.
• Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram are commonly used to treat various mental health conditions, including major depression, dysthymia, panic disorder, and obsessive-compulsive disorder 6.
• However, the use of SSRIs as add-on therapy for negative symptoms of schizophrenia has yielded conflicting results, with one meta-analysis finding no significant improvement in negative symptoms 7.

Considerations for Treatment

When selecting a medication, it is essential to consider the patient's specific condition, medical history, and potential side effects.

• Olanzapine has been associated with weight gain and an increased risk of type 2 diabetes and metabolic syndrome, which requires vigorous management 3.
• SSRIs can cause side effects such as gastrointestinal disturbances, headache, sedation, insomnia, and sexual dysfunction 6.
• The combination of olanzapine and fluoxetine has been found to be safe and effective, but double-blind studies are needed to confirm this impression 4.