Drugs- Mood Stabilizing Drugs and other treatments for Bipolar Disorder (Martin) Flashcards
DSM diagnostic criteria for manic episode
A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least one week and present most of the day, nearly every day (or any duration if hospitalization is necessary).
B) must meet 3 of the following (DIG FAST)
-Distractability
-irresponsibility - hedonistic- doesn’t care about consequences
(sexual indiscretion, foolish)
-grandiosity - inflated self esteem
-Flight of ideas
-Activity (increase in goal directed activity or agitation
-decreased need for sleep
-talkativeness
C) impairs social or occupational functioning or may necessitate hospitalization
D) not attributable to substance or other medical condition
what is the standard of treatment for bipolar disorder
lithium
but antiepileptic drugs such as valproate and carbamazepine are also widely used despite evidence that they are less effective in preventing recurrence.
treatment of acute mania or mixed episodes and maintenance of bipolar disorder
atypical or second generation antipsychotic drugs
treatment of depression associated with bipolar disorder
quetiapine
lurasidone
combo of olanzapine with fluoxetine
many studies have shown that lithium has protective effects against suicide and self-harm.
prevention of recurrent depression in bipolar disorder
lamotrigine (anticonvulsant)
MOA of lithium
Lithium is believed to attenuate signaling via receptors coupled to the phosphatidylinositol bisphosphonate (PIP2) second messenger pathway (see figure below). Lithium interferes with the resynthesis of PIP2, leading to its relative depletion in neuronal membranes of the CNS. PIP2 levels in peripheral membranes are unaffected by lithium. Thus, lithium disrupts the IP3/DAG intracellular signaling pathway. Lithium is also known to inhibit glycogen synthase kinase-3 (GSK-3) a kinase that pays a role in several different intracellular signaling pathways. Additional effects on adenylyl cyclase activity, G proteins, and protein kinase C activity have been described but the relevance of all these findings is not clear. Li+ substitutes for Na+ ion in generating action potentials and in Na+-Na+ exchange across membranes but does not affect Na+-Ca++ exchange or the Na+,K+ ATPase pump.
Both lithium and valproate may take days to weeks to have a full therapeutic effect; acutely manic patients often require what?
an antipsychotic drug or additional temporary treatment with a benzodiazepine.
Antidepressants should be tapered and discontinued during a manic episode.
which drugs decreases the risk of recurrent manic and depressive episodes.
lithium alone OR in combo with valproate, carbamazepine, or lamotrigine
what should you do before starting lithium
what about when you want to stop lithium
kidney function tests
- creatinine
- urine specific gravity
thyroid function tests
repeat kidney function tests every 1-2 times per year
• Rapid discontinuation of lithium increases the risk of relapse and possibly suicide, so lithium may need to be tapered slowly over 3 months if it is to be discontinued after long-term maintenance.
signs of lithium toxicity
tremor dysarthria, delirium, coma, seizures, and autonomic instability.
what causes increased reabsorption of lithium
• Volume depletion or renal impairment from any cause increases lithium reabsorption. Examples of such conditions include gastrointestinal losses, acute decompensated heart failure, cirrhosis, and the administration of diuretics, NSAIDs, or angiotensin converting enzyme inhibitors.
ADR’s of lithium
LMNOP
M movement- tremor- add B- blocker (propranolol)
N- nephrogenic diabetes insipidus *polyuria
O-hypOthyroidism- goiter, can cause acute exacerbations of bipolar illness
P-pregnancy problem
Nausea and fatigue may occur in the first days to weeks of treatment with lithium, even when serum concentrations are in the recommended range. Tremor, thirst, polyuria, edema and weight gain may persist for the duration of treatment.
what substances can decrease the concentration of lithium
caffeine
theophylline
Lithium contraindications
Lithium use during pregnancy has been associated with congenital cardiac abnormalities. High neonatal lithium concentrations are a risk factor for lower Apgar scores, longer hospital stays, and reversible neurologic toxicity that could be minimized or avoided by withholding maternal lithium for 24 hours before delivery.
what are the three types of lithium toxicity (poisoning) that can occur
Lithium poisoning may be (1) acute, as occurs when a patient who is not on lithium therapy ingests a bottle of lithium tablets in a suicide attempt; (2) acute-on-chronic, as occurs when a patient who is on lithium therapy also ingests a large number of lithium tablets all at once; or (3) chronic, as occurs when a patient on a stable lithium regimen suffers a reduction in renal function.
monitoring of lithium levels?
Use of lithium requires monitoring to maintain serum concentrations within the therapeutic range and avoid toxicity. Lithium has a very narrow therapeutic index (~2). Concentrations should be measured about 12 hours after the last dose. For acute treatment, target serum concentrations are 0.8 to 1.0 mEq/L. For maintenance, serum concentrations should be between 0.6 and 1.2 mEq/L. Renal function and thyroid function should be monitored routinely in patients taking lithium. Usually an initial assay of lithium serum concentration is performed at about 5 days after beginning therapy with lithium, i.e., after a steady-state serum concentration has been obtained. This process of determining plasma levels should be repeated anytime a dosage change occurs. Plasma lithium levels should be routinely monitored until predictable and effective levels of the drug have been established and then monitoring at longer intervals can be employed.
what is divalproex
valproic acid and sodium valporate
what pt’s is valproate best used in
best for patients with mixed episodes or for patients with rapid-cycling bipolar disorder
Valproate seems to be more effective for treating manic episodes than depressive episodes
Valproate may also be more effective in preventing manic relapses than in preventing depressive episodes.
MOA of valproate
The proposed mechanism of action for valproate include blockade of voltage-dependent sodium channels, increased GABA levels via blockade of GABA transaminase, and inhibition of T-type calcium currents.
ADRs of valproate
sedation
weight gain
GI upset
monitor liver function due to elevation in hepatic transaminases
hair loss
CI in pregnancy - neural tube defects
thrombocytopenia
increases polycystic ovarian syndrome in women up to nine fold
carbamazepine
MOA and use
• Carbamazepine is approved for the treatment of bipolar disorder. It is not as useful for patients who do not wish to or cannot comply with blood testing and close monitoring. It can be used in combination with lithium, valproate, or atypical antipsychotics.
MOA:These drugs reduce the propagation of abnormal impulses in the brain by blocking reactivation of voltage-dependent sodium channels,
induction of cytochrome P450’s
ADR’s of carbamazepine
rash
dizziness, diplopia
nausea, headache, somnolence
hyponatremia
Rare and serious:
aplastic anemia, agranulocytosis, SJS
continuously monitor blood counts
CI in pregnancy
Lamotrigine MOA
- Lamotrigine is FDA-approved for the maintenance treatment of bipolar disorder.
- Lamotrigine blocks sodium channels as well as high voltage-dependent calcium channels.
ADR’s of lamotrigine
dizziness and ataxia
somnolence, headache
diplopia, nausea, vomiting
rash
insomnia
About 10% of patients develop mild rash; severe, life-threatening rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis, has occurred rarely.
