Bipolar usually associated with other positive psychotic

Bipolar disorder also called manic depressive illness,
it is a complex, recurrent, and severe mood disorder. There are over 350
million diagnosed cases worldwide (Whiteford, H.A. et al., 2013). The world health organization defines
it as a psychiatric mood disorder which is characterized by its complexity that
range between two different mood extremes, a maniac or extremely elative mood
to a severely depressive one, and usually associated with other positive
psychotic symptoms such as delusion or hallucination (Whitfield,

According to Cooper’s guidelines for psychiatric
illnesses classifications,  Bipolar disorder is
differentiated into four subtypes based on the symptoms: manic or mixed episode that can be
associated with psychosis and/or major depression is called Bipolar I, major depression with hypomanic episode as well as no
history of manic or mixed episode is called Bipolar II, hypomania and depressive symptoms that do not meet criteria
for bipolar II disorder is called Cyclothymic disorders, and the fourth subtype
is depressive episodes but not major illness associated with non-specified
episode as it does not meet criteria for major depression, bipolar I disorder,
bipolar II disorder, or cyclothymia (Cooper,

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According to International classification of
disease (ICD101) and diagnostic and statistical manual of mental disorders (DSMI)
for Mental Illnesses classifications and definitions, the detection of bipolar
disorder needs that a person has undergone (experience) one or more episodes of
mania with or without episodes of depression during his/her life history, in
order to distinguish bipolar disorder from the more common form of mood disorder
in the population, in which it is called a unipolar disorder where patients
undergo one or more episodes of depression without no episodes of elevated mood
in a pathological terms at all (Bell, 1994) and (Whitfield, 1993). Usually, depressive
episodes’ manifestation can occur with no associated mixed, manic, or hypomanic
episode in which final diagnosis has to be postponed. A very important
question has to be asked by a psychiatrist if unipolar disorder is suspected.
He/she has to ask a patient whether he/she has ever expressed any symptom of
mania or hypomania such as changes in energy, racing thoughts, insomnia, or an
elevated mood that was distinctly better than usual for a brief period in the
past (Manning, J.S., 2010).

However, bipolar patients are usually known to be drug
users. Some have been related with morbidity, 15 % have died as a result of
suicide attempt (Manning, J.S., 2010). That is why it is important that
patients and their families should be educated about mood relapse, suicide
commitment, and the effectiveness of early intervention to reduce complications,
or frequency of hospitalization visits (Parikh, S.V.,2010). Treatment
for manic and depressive phase of illness are available (Gardner, H.H. et
al., 2006).

          As World Health Organization stated, bipolar disorder is not
related to race gender, or ethnicity. Although it has no specific age, but more common in persons
younger than 25 years (Merikangas, K.R. et al., 2007). Commonly,
Bipolar patients have other mental disability like anxiety disorders, impulse
control and attention -deficit/hyperactivity disorders (ADHD), and substance
abuse, which may lead to worse outcome (Parikh, LeBlanc and Ovanessian, 2010). Moreover, Other chronic physical
illnesses such as diabetes mellitus, obesity, and cardiovascular disease are more
common in this category of psychiatric patients (Fiedorowicz, J.G. et al.,
2009). Medications used to treat bipolar disorders may increase
susceptibility to metabolic syndrome, patients with untreated bipolar disorders
have significantly higher rates of death from cardiovascular causes (Fiedorowicz,
J.G. et al., 2009). As reported, residual mood symptoms between episodes and
abnormal circadian rhythm in bipolar patients have been associated with the lack
of social bolster and high level of social tense (Judd, L.L. et al., 2002).

It has been noticed that during depressive or mixed
state (i.e., depressed mood combined with increased energy, restlessness, and
racing thoughts), patients usually attend the clinic for a treatment (Judd, L.L. et al., 2002).

Taking Marzani-Nissen’ guidelines into
count, other causes of mood disturbance in a patient who is suspected to be
bipolar have to be ruled out before making a diagnosis with Bipolar disorder.
Causes of mood disturbance are vary from substance abuse, medications used for
other chronic physical and psychiatric illnesses as well as multiple physical
conditions. Alcohol, amphetamines, cocaine, hallucinogens, opiates are
substances that can lead to mood disturbances. Cardiovascular medications
(captopril, hydralazine Endocrine: bromocriptine, corticosteroids), Neurologic
agents (levodopa), Psychiatric agents (antidepressants, disulfiram,
methylphenidate, monoamine oxidase inhibitors), and other agents: baclofen, cimetidine
have been linked to mood disturbance. Collagen vascular diseases and systemic
lupus erythematosus, Endocrine diseases (Cushing disease, hyper- or
hypothyroidism), Infectious diseases ( herpes encephalitis, human
immunodeficiency virus encephalitis, influenza, neurosyphilis), Neurologic
diseases (complex partial seizures, Huntington chorea, migraine headache,
multiple sclerosis, neoplasm, stroke, traumatic brain injury and Wilson
disease) Vitamin deficiency (B12, folate, niacin, thiamine and can assist in
selecting a medication) can cause mood disturbances (Price, A.L. &
Marzani-Nissen, G.R.,2012).

Treatment options include: psychotherapy, mood stabilizers and neuroleptic
drugs {14,15}. Medication selection depends on the
presenting phase of illness, but the earlier recognition and medical
intervention improves the outcome by improving patients’ response to medications
into a double and decrease risk of relapse (Cooper, 2001). Relapse follows in the first year
of the disease in one third of patients and can occur in five years from the
time of diagnosis in 70 % of patients. This fact was beyond the reason why all
bipolar patients always have to be on treatment. (Relapse and
impairment in bipolar disorder, 1995). Regular follow up with a
psychiatrist are often needed because of a chance of disorder relapse, drug
resistance, suicide behavior and other comorbidities (Relapse
and impairment in bipolar disorder, 1995).






Valproic acid (VPA), is
considered as broad-spectrum antiepileptic drug (AED). It is helpful for
many psychiatric illnesses like epilepsy, variety of psychiatric symptoms,
including bipolar, borderline personality disorder (BPD) and migraine. It is
also used in patients with alcohol withdrawal symptoms. It promotes
postsynaptic transmission of gamma-aminobutyric acid (GABA) as well as it can decrease degradation of GABA (Cattaneo, C.I. et al.,

Valproic acid has different formulation such as: oral
preparation and intravenous formulation. Therapeutic daily doses range from 1 to 2 g in
adults, and from 15 to 60 mg/kg in children (Hardman
JG Ed., Limbird LE Ed.,et  al.1996). Therapeutic serum concentrations
range starts from 50 up to 125 ?g/ml (Hardman JG Ed., Limbird LE Ed.,et  al. 1995) and (Chadwick, D.W., 1985). Valproic acid therapeutic
concentrations is highly bound to plasma proteins (80–90%), but the percentage
decreases at higher VPA levels (Hardman JG Ed., Limbird LE Ed.,et  al. (1996).

Fatigue, gastrointestinal disturbances, weight gain,
tremors, hair loss, thrombocytopenia, polycystic ovary syndrome, changes in
hepatic or renal functions, teratogenicity, and rarely hyper-ammonemic encephalopathy
have been recorded as adverse effects of valproic acid treatment (Nanau, R.M. & Neuman,
M.G., 2013). The first months of VPA chronic dose may be accompanied with
elevation in transaminase which may lead to hepatotoxicity in 44% of patients.
May occur in the first 6 months. Once patient stops having VPA, it usually resolves
completely (Ishikura, H. et al., 1996).

The clinical presentation of hepatotoxicity includes:
lethargy, jaundice, nausea, vomiting, hemorrhage, anorexia (Ishikura, H. et
al., 1996). Histological changes are similar to those observed in the
Reye’s syndrome, with early production of microvesicular steatosis followed by
development of centri-lobular necrosis (Ishikura, H. et al., 1996).

Some conditions like: children under 24 months especially
those with organic brain disease, patients having developmental delay,
coincident congenital metabolic disorders, previous liver dysfunction, or
severe epilepsy treated with polytherapy or ketogenic diets are considered as
risk factors that can affect the judgment of the psychiatrist whether to put
the patient on VPA or not (Ishikura, H. et al., 1996).

Patients who
receive valproic acid should undergo regular monitoring of blood concentration
to ensure it is within the therapeutic range, hepatic, renal function and in
women who have developments of polycystic ovaries and side effect. The
benefit:risk balance of valproic acid should be regularly reassess.