General Information

Saphris (asenapine) is a sublingual psychotropic agent. The exact mechanism of action is unknown. However, it has been suggested that the efficacy of asenapine in schizophrenia is mediated through a combination of antagonist activity at D2 and 5-HT2A receptors.

Saphris is specifically indicated for the acute treatment of schizophrenia in adults and for the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults.

Mechanism of Action

Saphris (asenapine) is a sublingual psychotropic agent. The exact mechanism of action is unknown. However, it has been suggested that the efficacy of asenapine in schizophrenia is mediated through a combination of antagonist activity at D2 and 5-HT2A receptors.

Side Effects

Adverse events associated with the use of Saphris for schizophrenia may include, but are not limited to, the following:

• insomnia
• somnolence
• extrapyramidal symptoms
• akathisia
• constipation
• oral hypoesthesia
• vomiting
• dizziness

Adverse events associated with the use of Saphris for bipolar disorder may include, but are not limited to, the following:

• somnolence
• headache
• dizziness
• extrapyramidal symptoms
• insomnia
• weight increased

Dosing/Administration

Saphris is supplied as a tablet for sublingual administration.

The recommended initial dose of the drug for schizophrenia is as follows:
Usual Dose for Acute Treatment in Adults
The recommended starting and target dose of Saphris is 5 mg given twice daily. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies.
Maintenance Treatment
There is no available evidence regarding how long the schizophrenic patient should remain on Saphris. It is generally recommended that responding patients be continued beyond the acute response.

The recommended initial dose of the drug for bipolar disorder is as follows:
Usual Dose for Acute Treatment in Adults:
The recommended starting dose of Saphris is 10 mg twice daily. The dose can be decreased to 5 mg twice daily if there are adverse effects. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials.
Maintenance Treatment
There is no available evidence regarding how long the bipolar patient should remain on Saphris. It is generally recommended that responding patients be continued beyond the acute response.

Clinical Trial Results

The FDA approval of Saphris was based on the following studies:

Schizophrenia
Three fixed-dose, short-term (six-week), randomized, double-blind, placebo-controlled and active-controlled (haloperidol, risperidone, and olanzapine) trials enrolled adult patients who met DSM-IV criteria for schizophrenia and were having an acute exacerbation of their schizophrenic illness. The primary efficacy rating scale was the Positive and Negative Syndrome Scale (PANSS). The primary endpoint was change from baseline to endpoint on the PANSS total score.
Trial 1
This study enrolled 174 subjects and compared Saphris (5 mg twice daily) to placebo. Saphris was statistically superior to placebo on the PANSS total score.
Trial 2
This trial enrolled 448 subjects and compared two fixed doses of Saphris (5 mg and 10 mg twice daily) to placebo. Saphris 5 mg twice daily was statistically superior to placebo on the PANSS total score. Saphris 10 mg twice daily showed no added benefit compared to 5 mg twice daily and was not significantly different from placebo.
Trial 3
Saphris could not be distinguished from placebo; however, an active control in this trial was superior to placebo.

Bipolar disorder
Two similarly designed, three-week, randomized, double-blind, placebo-controlled and active-controlled (olanzapine) trials enrolled adult patients who met DSM-IV criteria for bipolar 1 disorder with an acute manic or mixed episode with or without psychotic features. The subjects received placebo or Saphris, initially administered 10 mg twice daily. The dose could be adjusted within the dose range of 5 to 10 mg twice daily from day 2 onward based on efficacy and tolerability. Ninety percent of patients remained on the 10 mg twice daily dose. Saphris was statistically superior to placebo on the YMRS total score and the CGI-BP Severity of Illness score (mania) in both studies.