Mood Stabilizers to Combat Bipolar Depression

Introduction

Psychological balance is important for our daily activity and healthy lifestyle. Around one percent of the world's population suffers from the major psychological disorder known as bipolar disorder. This chronic disorder is responsible for major episodes of depression in more than 40 million people in the world. Drugs like mood stabilizers can be effective in such cases.

What Is Bipolar Disorder?

Bipolar disorder is a mental illness characterized by major or rapid changes in emotions and mental emotions. The other names for this disorder are manic-depressive illness or manic depression. This is one of the major causes of psychological disabilities in the world, along with mental problems.

Pathophysiology: The exact causative factors involved in bipolar disorder are not known. According to some researchers, the neurobiological changes in the brain are responsible for such pathologies. In most cases, genetic factors are involved in such conditions. Changes in genes like CACNA1C, ODZ4, and NCAN. Also, chromosomal changes and changes in the DNA are associated with it. Such changes often have a familial history. Apart from this, the effects of external factors like stress, trauma, and drugs play a pivotal role in the pathogenesis of this disorder. All these factors lead to changes in the body. Changes like increased inflammation and oxidative stress lead to neural function abnormalities. Also, changes in neurotransmitters like serotonin and dopamine. Also, the functioning of the neurons is altered. In bipolar disorder patients, the low-level and dysfunctional activity of gamma-amino-butyric acid (GABA) is observed. Apart from this, changes in the other factors like brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, and neurotrophin-4

Symptoms: The symptoms of bipolar disorder are numerous. However, such symptoms usually appear during late teenage years. Symptoms may vary according to the type of bipolar disorder the person is suffering from. The person may experience emotional imbalance characterized by anxiousness, irritability, sadness, and frequent changes in emotions. Also, symptoms like sleep irregularities, hunger problems, and inactivity can be observed. On the basis of symptoms, different types of bipolar disorders are;

• Bipolar I Disorder: In this condition, patients may experience manic episodes. Such episodes may last more than seven days. Also, symptoms of depression may be present in such cases. In a year, there should be four or more episodes of mania or depression.

• Bipolar II Disorder: In this condition, symptoms of depression are observed.

• Cyclothymic Disorder: In this condition, recurrent episodes of hypomanic and depressive symptoms are seen. However, symptoms are not severe in such cases.

What Are Mood Stabilizers?

Mood stabilizers are a group of drugs that are used to treat bipolar disorder. These drugs are used to treat manic and depressive episodes associated with bipolar disorder. These drugs can also be used as prophylactic drugs or in the treatment of depression. Before starting mood stabilizers or any other pharmacological agents, proper evaluation of the patient is necessary. Associated psychotic disorders needed to be identified. Before starting the treatment, the proper medical condition of the patient should be evaluated, and other comorbid conditions should be evaluated. Pharmacological treatment or other mood treatment should only be considered in patients suffering from severe symptoms or conditions like malnutrition, violence, and suicidal tendencies.

What Are the Different Types of Mood Stabilizers?

Mood stabilizers can be grouped into first and second generations. The first-generation mood stabilizers were introduced in the 1960s and 1970s. The drugs belonging to this group are Lithium, Valproates, and Carbamazepine. In the 1990s, the second generation of mood stabilizers was introduced. The drugs belonging to this group are Clozapine, Olanzapine, Quetiapine, and Lamotrigine. Apart from this, some drugs are used as adjuvant drugs for mood upliftment. These drugs are known as insufficient mood stabilizers. The drugs belonging to this group are Asenapine, Topiramate, and Pregabalin.

• Lithium: G-proteins are the molecules on the cell surface that help signal transportation. G-proteins, along with neurotransmitters, aid in the process of cellular signal transfer, cell growth, and differentiation. In patients with bipolar disorder, lithium is used to stimulate basal activity and inhibit stimulated adenylate cyclase. It also potentially results from the stabilization of the inactive G protein by lithium. Lithium is also responsible for the downregulation of polyphosphoinositide signaling by acting as an uncompetitive inhibitor of inositol monophosphatase and inositol polyphosphate 1-phosphatase. Lithium is the strongest drug used in bipolar disorder monotherapy for more than fifty years. The dosage of lithium should start with a minimum dose and should be increased gradually. This is also used in the treatment of classical mania, bipolar depression, and the predominant polarity of illness associated with depression.

• Valproate: Valproate or valproic acid can be used for the treatment or management of acute mania and mixed episodes. The potent compound belonging to this drug is Divalproex sodium. This drug can also be used as part of combination therapy or can be used in patients suffering from complex, partial, and simple seizures. This drug is responsible for the obstruction of sodium into neurons. This causes decreased firing potential and excitability of neurons. Valproic acid also has an inhibitory effect on neurotransmitters like GABA (gamma-aminobutyric acid). The degradation of GABA facilitates this action. Valproate also modulates various calcium channels responsible for neuronal signaling, neurotransmitter release, gene expression, and cellular survival. Inhibitory effects on certain calcium channels are responsible for reducing the excitability of neurons. In patients suffering from bipolar disorder, usually, a dosage of 250 to 500 milligrams three times a day is prescribed.

• Carbamazepine: Carbamazepine is used in patients suffering from bipolar disorder I. This can also be used as a combination drug in patients suffering from mixed episodes of bipolar disorder. This drug acts on the sodium channels and causes a decrease in neurotransmission and action potential of the neurons. This drug also acts on the G-protein-coupled receptors and is responsible for the modulation of neurotransmission. This drug also has inhibitory effects on the action of the enzyme adenylyl cyclase, which attenuates cyclic AMP-mediated signaling pathways. The dosage of this drug starts at 200 milligrams twice daily and gradually increases.

• Clozapine: This is an antipsychotic drug that is used mainly for the treatment of schizophrenia. In bipolar disorder, this drug is used to prevent recurrences in severe and drug-resistant cases. It can also be used along with lithium as a combination drug.

• Lamotrigine: This is an FDA (Food and Drug Administration) approved drug that is used in cases of bipolar disorder I or the maintenance phase of the therapy. This drug is effective in fighting cases of recurrent depression and rapid-cycling bipolar depression. This drug acts on the sodium channels and regulates presynaptic glutamate and aspartate release. The release of the neurotransmitters is also regulated by this drug.

What Are the Side Effects of Mood Stabilizers?

The side effects of mood stabilizers are;

1. Lithium may have harmful effects on nephrons. It may cause renal dysfunctions. Also, it is associated with thyroid problems and unnatural weight gain.

2. Valproic acid is associated with gastrointestinal problems and hepatic (liver) dysfunctions. Loss of hair, tremors, and weight gain can also be observed in some cases.

3. Carbamazepine is associated with nausea, vomiting, and drowsiness. Severe allergic reactions can be seen in some cases, Anemia and cardiac dysfunction can be seen in some cases also,

4. Lamotrigine may be responsible for skin rashes and tremors.

Conclusion

Bipolar disorder is a serious psychological disorder. Mood stabilizers are effective in preventing manic and depressive episodes of bipolar disorders. These drugs regulate the balance of the neurotransmitters and control the neural signaling pathways. However, due to severe systemic side effects proper medical evaluation of the patient is necessary to overcome any complications.