Double-Blind Placebo Controlled Study of Adjunctive Aripiprazole for Symptomatic Hyperprolactinemia In Premenopausal Women With Schizophrenia
Double-Blind Placebo Controlled Study of Adjunctive Aripiprazole for Symptomatic Hyperprolactinemia In Premenopausal Women With Schizophrenia
Prolactin is a hormone that naturally occurs in the body. Some women taking antipsychotic
 medications may have high levels of prolactin in their bodies. High levels of prolactin may
 cause women to have problems with sex or satisfaction from sex. It may also cause women to
 have fewer or no menstrual periods. It may also cause the production of breast milk and may
 contribute to long term bone loss.

 In this study, the investigators are testing whether taking adding a low dose of an
 antipsychotic medication called aripiprazole may help improve high prolactin levels and help
 with sexual dysfunction or problems with menstrual periods. The investigators are also
 looking to see if it may slow the loss of bones. This medication has been shown to be helpful
 for improving symptoms of schizophrenia.
This will be a 16-week, double blind, placebo controlled randomized trial of aripiprazole
 added to an existing stabilized regimen of antipsychotics (either risperidone or paliperidone
 oral or long acting injectable formulations) for treatment of elevated symptomatic prolactin
 levels. Aripiprazole dosing will begin at 5 mg/day once daily and increased to 10mg by mouth
 once daily at the end of week 2 and then increased to 15 mg/day once daily at the end of week
 8 in women who have not yet regained their menstrual period. If a woman gets her menstrual
 period on the 5 or 10 mg dose she will remain on this dose for the study. Women will remain
 on their current stabilized medication regimen during the course of the adjunctive trial of
 aripiprazole or placebo. Subjects will be able to receive anticholinergic medications as
 needed (e.g., benztropine and diphenhydramine) for extrapyramidal side effects, propranolol
 for akathisia, and benzodiazepines (e.g.,lorazepam) for agitation or anxiety.

 Participants will be assigned to either get aripiprazole or placebo (a sugar pill), this will
 be decided randomly with a 50-50 chance of receiving one or the other medication. The placebo
 will be sucrose filled capsules that are identical to the active medication. It is double
 blind so no one will know if the capsule is placebo or aripiprazole. The dosing will be the
 exact same, one capsule taken daily until week 8. At this time 2 capsules will be given if
 the participant dose not regains their menstrual period.
Inclusion Criteria:

 -  Subjects will be females of any race, with an age range of 18?50.

 -  Subjects will meet DSM-IV TR (APA, 2000) criteria for either schizophrenia,
 schizoaffective disorder, or bipolar disorder. A best estimate diagnostic approach
 will be utilized in which information from the Structured Clinical Interview for
 DSM-IV (First et al, 1997) is supplemented by information from family informants,
 previous psychiatrists, and medical records to generate a diagnosis

 -  Women will need to be taking a stable dose of antipsychotic regimen for at least two
 months and are considered to have stable symptoms by the treating psychiatrist. This
 regimen must include any form of risperidone or paliperidone.

 -  All women will have a prolactin level > 24 ng/ml (either identified at screening or
 from the past 6 weeks in the medical record)

 -  All women will have evidence of a prolactin related hormonal side effect (amenorrhea,
 oligomenorrhea or galactorrhea). This will be determined by patient report/history and
 medical record/clinician interview. Oligomenorrhea is defined as infrequent,
 irregularly timed episodic bleeding occurring at intervals of more than 35 days from
 the previous menstrual cycle and amenorrhea is defined as absence of menstruation for
 three menstrual cycles or 6 months (Berek et al. 2002). Galactorrhea is defined as
 lactation or copious milk secretion.

 -  Subjects must be judged competent to participate in the informed consent process and
 provide voluntary informed consent, by scoring a 10 out of 12 on the Evaluation to
 Sign Consent (ESC)

 Exclusion Criteria:

 -  Postmenopausal women will be excluded. Since it may be difficult to determine
 menopause in patients with amenorrhea, any women more than 45 years will be assessed
 for menopausal symptoms such as but not limited to or by: hot flushes, depression,
 excitability and fatigue. A medical doctor will advise on the menopausal status.

 -  Patients with a history of a pituitary tumor (microadenoma, macroadenoma, neoplasm)
 will not be included in the study. Previous medical records will be obtained if
 possible to examine prolactin levels and medical histories.

 -  Subjects with documented Cushing's disease, or who are pregnant or currently lactating
 post pregnancy will be excluded.

 -  Subjects who meet DSM-IV TR criteria for alcohol or substance abuse within the last
 month are excluded. Subjects with nicotine use or dependence will not be excluded.

 -  Medications which may increase prolactin or cause sexual dysfunction, including:
 metoclopramide, methyldopa, reserpine, amoxapine, droperidol, prochlorperazine,
 promethazine, bromocriptine, cabergoline, pergolide, There are many medications that
 may affect sexual function (not hormonal side effects) unrelated to dopamine
 transmission. These are only permitted as long as the subject has been receiving them
 for greater than 4 weeks (SSRIs, mood stabilizers, diuretics, antihypertensives,
 H2antagonists, bupropion). We allow these medications to enhance generalizability