By Hesamoddin Hosseinjani

Roozbeh Hospital

Department of Clinical Pharmacy

november 2013

ID: M.M. is a 40 years old woman, married, two

children, diploma degree, painting job, 2nd turn of

hospitalization due to psychiatric disorders.

CC: I hate my husband.

RFR (Reason For Referral): physical and verbal

aggression.

SOH: Patientʼs husband, brother and mother.

PI: ten days before admission, following the stressor of

confliction and arguing with her mother and husband, the

patient experienced exacerbation of symptoms including

irritable mood, aggression and destroying furniture,

talkativeness, dysphoric mood, agitation, decreased need for

sleep, decreased appetite, pessimism and hatred toward her

husband, requesting divorce, Increased energy and suicidal

idea.

PPH:

Her psychotic symptoms have begun from 4 years ago with

disturbance of sleep, Increased sexual desire and extramarital

relationship, excessive aggression, pessimism in regard with

her husband behaviors, abnormal behaviors like profligacy

(excessive shopping) and unusual makeup.

1st admission of the patient with the diagnosis of BMD in Army

hospital was in 1391 at age 39 (due to the her request for

more mental tranquility). 6 sessions of ECT were administered

on her at that time with favorable response.

Because of non compliance to administered drugs, the

mentioned symptoms have become worse gradually and

resulted in the recent admission of the patient to the

hospital.

PMH: right breast mass surgical resection.

DH: history of taking drugs irregularly without knowing

their names.

SH: cigarette smoking and addiction to alcohol.

Questionable crystal use.

FH: patientʼs husband had a diagnosis of MDD and was

using sertraline and lorazepam for 2 years.

Husband had a history of addiction to opium, crystal and

crack but has not used them anymore since 3 years ago.

PH:

1st marriage was in 1372 which resulted in divorce one year

later, the 2nd marriage with the present husband happened

after 2 years of friendship.

Although she is married, her extramarital relationship has

continued until the present time.

Before the exacerbation of her psychotic features in recent

years, except for occasional cases of arguing with her

husband, she was known as affectionate, talented and orderly

woman.

MSE:(at the time of interview)

General appearance:

Young woman with proportional Apparant age with

chronological one.

Appropriate eye contact and grooming.

Attitude: cooperative - defensive

Mood : dysphoric

Affect : Appropriate

Speech : tone NL (monotone) rate NL volume NL

Psychomotor : Agitated

Thought Content:

delusion pos Anhedonia pos

(persecutory & misidentification del)

Hopelessness neg thought of death neg

Helplessness pos Suicidal idea neg

Homicidal idea pos

phobia neg obsession neg

Perception :

Hallucination neg illusion neg

Cognition : alert with orientation to time, place and

person

Attention was OK Abstract thinking was OK

Concentration was OK judgement was OK

Memory was OK

Impulsivity : positive

Insight :partial

Physical Examination: normal

Vital Signs :

BP: 110/65 mmhg PR: 80 beats/min RR: 16 breaths/min

T:36.7 C

Laboratory data:

TFT, WBC , Plt, LFT, Renal function, U/A, FBS, Lipid profile:

Normal

RBC: 3.79 million/mcl hgb: 10.1 g/dl Hct: 32.3% MCV:85.2 fl

Viral markers & VDRL: neg

Bipolar Mood Disorder Type I (manic episode)

Consultation with Pharmacotherapy service

According to the diagnosis of BMD, which

therapeutic drug regimen will be the better choice

for the patient with consideration of breast

fibrocystic changes?

Drug list :

Tab Divalproex : 250 mg tds

Tab Quetiapine: 25mg bd (olanzapin 5mg hs D.C.)

Tab chlordiazepoxide: 5mg prn

Tab folic acid : 1mg daily

Tab ferrous sulfate: 2 tab daily

General Considerations:

Fibrocystic condition is the most

frequent lesion of the breast.

It is common in women 30–50 years

of age but rare in postmenopausal

women who are not taking hormonal

replacement.

Estrogen is considered a causative

factor.

Although fibrocystic condition

has generally been considered to

increase the risk of subsequent

breast cancer, only the variants

with a component of epithelial

proliferation (especially with

atypia) or increased breast

density on mammogram represent

true risk factors..

A. Symptoms and Signs

Fibrocystic condition may produce an asymptomatic mass in the breast that is discovered by accident, but pain or tendernessoften calls attention to it.

B. Diagnostic Tests

Mammography and ultrasonography should be used to evaluate a mass in a patient with fibrocystic condition.

Simple mastectomy or extensive removal of breast tissue is rarely, if ever, indicated for fibrocystic condition.

Pain, fluctuation in size, and multiplicity of lesions are the

features most helpful in differentiating fibrocystic condition from

carcinoma.

Final diagnosis, however, depends on analysis of the excisional

biopsy specimen or needle biopsy.

When the diagnosis of fibrocystic condition has been

established by previous biopsy or is likely because the history

is classic, aspiration of a discrete mass suggestive of a cyst is

indicated to alleviate pain and, more importantly, to confirm

the cystic nature of the mass.

Hormone therapy is not advisable, because it does not cure the

condition and has undesirable side effects.

Danazol (100–200 mg orally twice daily), a synthetic

androgen, is the only treatment approved by the US Food and

Drug Administration (FDA) for patients with severe pain.

Androgenic effects (acne, edema, hirsutism) usually make this

treatment intolerable; in practice, it is rarely used.

Similarly, tamoxifen reduces some symptoms of fibrocystic

condition, but because of its side effects, it is not useful for

young women unless it is given to reduce the risk of cancer.

Oil of evening primrose (OEP), a natural form of gamolenic

acid, has been shown to decrease pain in 44–58% of users.

Studies have also demonstrated a low-fat diet or decreasing

dietary fat intake may reduce the painful symptoms associated

with fibrocystic condition.

The risk of breast cancer developing in women with fibrocystic

condition with a proliferative or atypical component in the

epithelium is higher than that of the general population.

These women should be monitored carefully with physical

examinations and imaging studies.

The study was conducted to determine whether prolactin (PRL)

influences radiological features of benign breast lesions.

Prolactin plays an important role in develop­ment of different

benign breast lesions, including fibrocystic breast disease.

Prolactin significantly influenced radiological presentation of

benign breast diseases. The present findings support hypothesis

that hyperprolactinemia influences pathogenesis and maintains

of solid lumps.

Substantial epidemiological, clinical, and biological evidence now

exists confirming the role of prolactin in human breast cancer, and

this means that prolactin-induced mammary tumorigenesis is not a

rodent-specific phenomenon.

Several conclusions concerning this data can be made:

1. Prolactin is associated with increased breast cancer risk in

women.

2. Prolactin-induced mammary tumorigenesis is therefore not

species- or rodent-specific.

3. The mechanism of prolactin action on mammary tumor

growth and development is similar in rodent and human.

4. Drugs that increase prolactin may increase human breast

cancer risk.

Both animal and in vitro data suggest that prolactin is

involved in tumorigenesis by promoting cell proliferation,

increasing cell motility, and improving tumor vascularization.

Whereas prolactin and its receptor are found in normal and

malignant tissues, concentrations of both are generally higher

in malignant tissue.

Several studies have linked hyperprolactinemia to an increased

risk of breast cancer in women.

Most studies have shown that conventional antipsychotics are

associated with a two to tenfold increase in prolactin levels.

In general, second generation antipsychotics produce a lower

increase in prolactin than conventional agents.

Several epidemiological studies have investigated whether

female psychiatric patients receiving treatment with a higher

incidence of breast cancer but results have been conflicting.

However, the most recent and methodologically strong study,

found that antipsychotic dopamine receptor antagonists

conferred a small but significant risk of breast cancer.

This study was done to determine whether atypical antipsychotics,

when compared to typical antipsychotics, increase the risk of

breast cancer.

Compared to patients who only used typical antipsychotics,

exclusive using of atypical antipsychotics were not with an

increased risk of breast cancer.

It is generally accepted that D2 receptor antagonism plays a

key role in the treatment of positive symptoms of schizophrenia

as well as in the production of EPS and hyperprolactinemia-

related side effects.

The apparently low occupancy of D2 by clozapine and

quetiapine, however, may be readily explained by the fact that

these two antipsychotics rapidly dissociate from the D2

receptor.

Rapid dissociation from D2 receptors has been reported to be

necessary for an antipsychotic effect, but insufficient for

induction of EPS and hyperprolactinemia.

The relative risk for prolactin elevation in descending order is

risperidone, paliperidone, typical antipsychotics, olanzapine,

ziprasidone, quetiapine, clozapine followed lastly by

aripiprazole.

VPA has shown potent antitumor effects in a variety of in vitro

and in vivo systems, and encouraging results in early clinical

trials alone or in combination therapies, either with classical

cytotoxics, other molecular-targeted drugs or radiation in a

number of solid tumors.

Epigenetic drugs have chromatin as their target through

inhibition of Histone deacetylases and DNA methyltransferases

therefore, yet unspecific, they may act upon most or all tumor

types as deregulation of the methylation and deacetylation

machinery are a common hallmark of neoplasia.

VPA, indeed, reduced cell growth by inducing apoptosis

and/or cell cycle arrest in ERα positive breast cancer cells,

while it has no significant effect in ERα negative cells.

VPA is a powerful antiproliferative agent in estrogen-sensitive

breast cancer cells, making this drug of clinical interest as a

new approach to treat breast cancer.

In both ERα-positive and -negative malignant mammary

epithelial cells, VPA reprograms the cells to a more differentiated

and “physiologic” phenotype that may improve the sensitivity to

endocrine therapy and/or chemotherapy in breast cancer

patients.

This findings provide a rationale for the therapeutic use of this

agent in breast cancer, as “sensitizers” for endocrine therapy

and/or as antiproliferative and differentiative agent.

Tapering up drugs dosage:

Tab Divalproex : 250 mg I-II-I

Tab quetiapine 25mg : I-II

During hospitalization, the patient

underwent 9 sessions of ECT.

Discharge drug list:

Tab Divalproex : 250 mg I-II-I

Tab quetiapine 25 mg: II-II

Tab chlordiazepoxide: 5mg prn

Tab folic acid : 1mg daily

Tab ferrous sulfate: 3 tab daily

Thank you for your attention