Mania and bipolar disorder

Mania or bipolar disorder causes , hypothesis and pharmacotherapy

1. Mania – Bipolar disorder and related drugs - Preetam Palkar F.Y. M. Pharm AISSMS college of pharmacy

2. Mania Mania is a mental disorder marked by periods of great excitement or euphoria, delusions, and overactivity. It is usually associated with bipolar disorder. Bipolar disorder- a disorder associated with episodes of mood swings ranging from depressive lows to manic highs.

3. Symptoms Mood changes Sudden increase in energy and activity Rapid speech that is difficult or impossible to interrupt Impaired judgment Flighty thoughts or thoughts that jump from topic to topic

4. Stages of mania Stage I – Hypomania Stage II – Acute mania Stage III – Delirious mania

5. Hypomania Hypomania is a mild form of mania that may not be recognised as a significant symptom by those around the person experiencing it. While hypomania affects sleep and activity and may lead to increased impulsivity, it usually doesn’t require hospitalisation or cause psychosis.

6. Acute mania During acute mania, an individual may experience increased impulsivity that causes them to act in a way that is brash, inappropriate or promiscuous. People with acute mania will also likely have increased energy, get little to no sleep and talk very quickly, often jumping from topic to topic. They may experience some symptoms of psychosis, where they are not fully aware of or connected to reality

7. Delirious mania Delirious mania is the most severe of the three stages of mania. Its symptoms are similar to acute mania, with the addition of delirium. Delirium is temporary confusion and a decreased ability or inability to connect with reality. This stage can also involve a combination of mania and psychosis. Because delirious mania can be profoundly disorienting, many people experiencing it need to be hospitalised to prevent injury to themselves or others.

8. Aetiology- causes Biological theories Genetic hypothesis Biochemical theory Neuroendocrine disturbance Psychological theories Psychoanalytic theory Behavioural theory Cognitive theory Sociological theory

9. Biological theories Genetic Hypothesis Genetic factors are very important in predisposing an individual to mood disorders. The lifetime risk for the children of one parent with mood disorder is 27% and of both parents with mood disorder is 74% The concordance rate for monozygotic twins is 65% and for dizygotic twins is 15%

10. Biochemical theories Increased amounts of norepinephrine, serotonin and dopamine activity cause an elevation in mood and two phases of bipolar disorder whereas decreased amounts lead to depressed mood Neuroendocrine disturbance Mood is also affected by the thyroid gland. Approximately 5-10% of clients with abnormally low level of thyroid hormones suffer from a chronic mood disorder. Client with a mild , symptom- free form of hypothyroidism are more vulnerable to depressed mood than the average person.

11. Abnormalities of neuroendocrine such as decreased nocturnal secretion of melatonin, decreased levels of prolactin, FSH, testosterone and somatostatin and sleep- stimulation of growth hormones causes mood disorder in clients.

12. Psychological theories Psychoanalytical theories According to Freud depression results due to loss of a loved object and fixation in the oral sadistic phase of development. In this model, mania is viewed as a denial of depression. Behavioural theory This theory of depression connects depressive phenomena to the experience of uncontrollable events. According to this model, depression is conditioned by repeated losses in the past.

13. Cognitive theory According to this theory depression is due to negative cognitions which includes: Negative expectations of the environment Negative expectations of the self Negative expectations of the future These cognitive distortion’s arise out of a defect in cognitive development and cause of the individual to feel inadequate, worthless and rejected by others.

14. Sociological theory Stressful life events such as the loss of parents or spouse, financial hardship, illness, perceived or real failure and midlife crisis etc are factors contributing to the development of a mood disorder. Certain populations of people including the poor, single person , or working mothers with young children seem to be more susceptible than others to mood disorders.

15. Lithium carbonate MOA CNS Lithium replaces body sodium and is nearly equally distributed inside and outside the cells, this may effect ionic fluxes across the brain cells or modify the property of cellular membranes. Decrease presynaptic release of NA and DA without affecting 5HT release. Inhibit hydrolysis of inositol-1- phosphate to free inositol by inhibition of inositol mono phosphatase enzyme.

16. Other actions Inhibit action of ADH on DCT causing diabetes insipidus like state Insulin like action of glucose metabolism Leukocytes count is decreased Inhibit release of thyroid hormones resulting in feedback stimulation of thyroid through pituitary.

17. Kinetics Well absorbed orally , neither protein bound nor metabolised First distribute in extra cellular water , then enters cells and penetrate into brain Adverse effects Nausea , vomiting and mild diarrhoea, thirst and polyuria, fine treamors at therapeutic concentration CNS toxicity when plasma concentration rises producing tremors, giddiness, ataxia etc Treated with osmotic diuretic and sodium bicarbonate infusion promoting lithium excretion.

18. Alternatives to lithium

19. Sodium valproate MOA Prolongation of sodium channel inactivation Weak attenuation of calcium mediated T - current Enhance release of inhibitory transmitter GABA due to inhibition of GABA transaminase Blockage of excitatory NMDA glutamate receptor

20. First line treatment for mania Better safety profile than lithium. Divalproex , complex of valproic acid has better gastric tolerance Combination of valproate with atypical antipsychotic is highly efficacious in acute mania Combination of lithium and valproate may succeed in cases resistant to mono therapy of either drugs.

21. Carbamazepine MOA- Prolongation of sodium channel inactivation Less effective than lithium or valproate in acute mania. Due to strong enzyme inducing property, CBZ has many drug interactions causing problems in the use of other drugs Nevertheless, it is a valuable alternative to lithium

22. Lamotrigine MOA- Prolongation of sodium channel inactivation It is not effective for treatment as well as prevention of mania Extensively used in maintenance therapy of type II bipolar disorder ( major depressive episode) Combination with lithium increases it’s efficacy.

23. Atypical - second generation antipsychotics (SGA’s) Olanzapine Risperidone Quetiapine Aripiprazole

24. MOA- weak D2 blocking but potent 5-HT 2 antagonistic activity With or without BZD they are used as first line drugs to control acute mania In emergency cases parental i.m. Olanzapine or haloperidol are most effective. Not used for long term therapy due to high risk of weight gain, hyperglycaemia,etc .