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Evidence based pharmacotherapy of major depressive disorder

Lifetime prevalence of MDD is 16.2% but most patients are not adequately treated. SSRIs demonstrate equal efficacy with older drugs but are better tolerated and accepted. 

NSRIs are slightly more efficacious 63% vs 59% for traditional SSRIS. 

The more severe the depressive symptoms, the more robust the response.

Review of several studies report a DECREASE in the rate of suicide and ideation with prescriptions of antidepressants.  The studies where depression was not the only diagnosis but included use of antidepressants for other clinical indications may show   higher rates. 

Studies show a true antidepressant reponse can occur within the first 1-2 weeks of treatment. 75% of patients respond by week 4. 

Factors predictive of risk of relapse: prior episode, more severely ill, and the  presence of residual symptoms.

TRD treatment strategies: switching to another medication.  25%,  Switching to a third medication 14%, and switching to another class demonstrate and additonal  13% improved. 

Augmentation strategies: add mirtazapine- (45%), bupropion (30%), buspirone, atypical antipsychotics, lithium, lamictal, T3, or SAMe. The most research has been with atypicals, lithium, and thyroid augmentation. 

Other possible treatments include :  Agomelatine- a melatonin receptor agonist and a 5-HT2c antagonist, and Glutamatergic agents. 

Glutamatergic agents: NMDA receptor antagonists – include memantine and ketamine. Riluzole-currently treats ALS and acts to increase  release of glutamate and block reuptake-with some additional promise in treating TRD. 

Pramipexole- pre-synaptic dopamine agonist. 

Modafinil-good for depression related fatigue and sleepiness. 

SSRI agents

Fluoxetine or Prozac- both a SERT blocker and 5HT2c blocker. also a weak blocker at the NET transporter. Inhibitor of CYP 2D6 and 3A$. Because of action on the 5HT@c receptor can be activating and has anti bulimic activity.

Sertraline or Zoloft – SERT inhibition and weak DAT inhibition. Also has some affinity for the sigma 1 receptor which may have both anxiolytic as well as antipsychotic properties. weak inhibition of CYP 2D6. calming antidepressant.

Fluvoxamine or Luvox – also acts on the sigma 1 receptor to a greater degree than sertraline . Inhibitor of CYP 1A2 and 3A4. Has indication for OCD and Social anxiety disorder.

Paroxetine or Paxil – weak NET inhibitor. mild anticholinergic activity. inhibits the enzyme nitric oxide synthetase therefore problem with sexual dysfunction. Inhibitor of 2D6 and also a substrate. Withdrawal when stooping abruptly. calming. helpful with IBS because of anticholinergic activity. 

Citalopram or Celexa- mild antihistaminic property. weak inhibition at CYP 2D6. the R enantiomer is the reason for this. 

Escitalopram or Lexapro- pure SERT inhibition. more potent and less sedating than celexa. 

Norepinephrine Facts to Know

Synthesized from the amino acid tyrosine

In the neuron tyrosine is acted upon by 3 key enzymes.

Tyrosine hydroxylase converts tyrosine into DOPA

DOPA decarboxylase coverts DOPA into dopamine

Dopamine beta hydroxylase converts dopamine to norepinephrine
Action is terminated both by enzymes : MAO located in mitochondria in the presynaptic neuron and COMT located outside the nerve terminal, and a transport pump that removes NE from the synapse and pumps back into the presynaptic neuron for future use. The pump is a site where many drugs work.

Norepinephrine receptor subtypes

NET pump

VMAt2 -packing into vesicles

Alpha 1

Alpha 2a

Alpha 2b

Alpha 2c

Beta 1

Beta 2

Beta 3
Only alpha 2 receptors are presynaptic autoreceptors. Act as a break stopping further NE release.

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Categories: Uncategorized
Norepinephrine facts to know
Synthesized from the amino acid tyrosine
In the neuron tyrosine is acted upon by 3 key enzymes.
Tyrosine hydroxylase converts tyrosine into DOPA

Sheri Spirt, M.D.
Ssdr18@aol.com
Please follow me on Twitter @DrSheriSpirt
www.drsherispirt.com
212 595-6901
16 East 96th Street Unit 1A New York, N.Y. 10128

CONFIDENTIALITY NOTICE: This communication, including attachments, is for the exclusive use of the person to whom it is addressed. The information contained in this transmission is confidential and may be privileged and/or contain confidential health information that is legally protected by state and federal law, including the Health Insurance Portability and Accountability Act of 1996 and related regulations. If you receive this message in error, please contact the sender by return e-mail, indicate that you are not the intended recipient, and confirm that you have deleted the original message. Use, disclosure, distribution or copying of documents transmitted to you in error is strictly prohibited. Please do not retransmit the content of this message.

Bipolar Spectrum Disorders

Bipolar 1/4 – designates an unstable form of unipolar depression that responds rapidly but is unsustained to antidepressants. They benefit to an addition of a moodstabilizer.

Bipolar 1/2- similiar to schizoaffective illness or coined schizobipolar.

Bipolar 1 1/2 – Hypomania without depression.

Bipolar II1/2 – cyclothymic patients that develop a major depressive episode.

Bipolar III – patients that develop a manic or hypomanic episode on an antidepressant.

Bipolar III 1/2 – Bipolar disorder with substance abuse.

Bipolar IV – association of depressive episodes with a pre-existing hyperthermia temperament. Hyperthermic patients are those with sunny outgoing personalities, and usually quite successful, that plunge into depression.

Bipolar V – depression with mixed hypomania.

Bipolar VI – bipolarity in the setting of dementia.

Dysphoria mania – mania with some depressive symptoms.

Tags:

Categories: UncategorizedBipolar Spectrum Disorders
Bipolar 1/4 – designates an unstable form of unipolar depression that responds rapidly but is unsustained to antidepressants. They benefit to an …
Sheri Spirt, M.D.
Ssdr18@aol.com
Please follow me on Twitter @DrSheriSpirt
www.drsherispirt.com
212 595-6901
16 East 96th Street Unit 1A New York, N.Y. 10128

CONFIDENTIALITY NOTICE: This communication, including attachments, is for the exclusive use of the person to whom it is addressed. The information contained in this transmission is confidential and may be privileged and/or contain confidential health information that is legally protected by state and federal law, including the Health Insurance Portability and Accountability Act of 1996 and related regulations. If you receive this message in error, please contact the sender by return e-mail, indicate that you are not the intended recipient, and confirm that you have deleted the original message. Use, disclosure, distribution or copying of documents transmitted to you in error is strictly prohibited. Please do not retransmit the content of this message.

Correlation of Hyperhomocysteinemia and Bipolar Depression

Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitamin B12, have antidepressant effect. Both depression and elevated HCY can increase cardiovascular risk. In this study, clinical and biochemical factors, including markers of endothelial function, in relation to hyperhomocysteinemia, in patients with bipolar depression during acute episode were studied. Method: One hundred and twelve patients (24 male, 88 female), aged 20-78 (mean 51 ± 14 years), with depressive episode in the course of bipolar mood disorder have been included. The assays were made of serum concentrations of HCY, vitamin B12, folic acid as well as markers of endothelial function such as E-selectin and intracellular adhesion molecule-1 (ICAM-1). Results: Hyperhomocysteinemia (>15 mM) was found in 50 patients (45%), significantly more frequently in male (67%) than in female subjects (39%). Female patients with hyperhomocysteinemia were significantly older than the remaining ones. A significant inverse correlation between HCY level and concentration of folic acid and vitamin B12 as well as with E-selectin and ICAM-1 was observed. Conclusion: The results point to a significant prevalence of hyperhomocysteinemia in bipolar depressed patients during an acute episode. They also corroborate the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid. An unexpected finding of negative correlation of HCY level with markers of endothelial functions in such patients is discussed in view of current concepts of the role of HCY in various conditions.

Trichotillomania

Trichotillomania is described as the recurrent pulling out of one’s own hair, leading to alone is and marked impairment. It is included under the OCD type disorders in the DSM-V. The other disorders now in that category include body dysmorphic disorder, hoarding disorder, excoriation disorder, and OCD. The lifetime prevalence is estimated at around .6% with a  F:M ratio of 4:1. The typical age of onset is between 10-13 years. The pulling can be automatic or focused. Over 20% of patients also experience trichophagia. Only 1/3 of patients with the disorder seek treatment. The disease is highly comorbidies with other psychiatric disorders, particularly those in the. OCD spectrum. Stimulants can make the pulling worse. It is also associated with rare variations in the SAPAP3 gene and does show a familial pattern. Treatments include psychotherapy, usually behavioral using habit reversal techniques (self monitoring, awareness training, competing response training, and stimulus control procedures) and pharmacotherapy (clomping mine, antipsychotic medications, and glutamate rigs agents). Among the glutamatergic agents, N-acetyl cysteine (NAC) has demonstrated benefit in a double blind PC trial…at a dosage of 200 mg. twice a day. Other agents worth noting include  olanzapine.  SSRIS have not yet shown to be that effective, adn fluvoxamine may be the drug of choice. 

Ketamine

Ketamine is a non competitive, N-methylfolate-D-aspartame glutamate receptor antagonist that is approved as an anesthetic agent. Recent studies have shown a rapid onset (2-24 hours post infusion) of antidepressant effect. This effect is short lived, with range of effect form 3-17 days. Studies have found twice weekly dosing to be sufficient over a 4-6  week period. The dose was .5mg/kg. Side effects included headache, dizziness, and nausea as well as acute transient psychotomimetic and dissociative symptoms which resolved within 2 hours. At this time, however studies over efficacy for longer time periods is needed. 

SSRIS with statins. Better or worse?

Now strategy for the treatment of treatment resistant depression has been the addition of anti-inflammatory agents, including COX-2 inhibitors, aspirin, and NSAIDS. Statins, used primarily for their lipid lowering properties also have direct anti-inflammatory effects. FIndings: concomitant use of an SSRi and a station was associated with a decreased risk for both psychiatric and general medical hospital contacts.  It was also NOT associated with increases in mortality. Over 870,000 patients were included in the study. 

Substance abuse and sleep issues? some things to know

It has been reported that almost 90% of people that abuse alcohol have sleep disturbances. other problems also exist for abuse of marijuana, cocaine, pain killers, caffeine, and nicotine.  Substance use leads to disruption in a number of neurotransmitters including acetylcholine, GABA, glutamate, norepinephrine, and orexin.

Alcohol can promote sleep but leads to fragmented restless sleep. There is also a decrease in total REM percentage and prolongation in REM onset latency. Alcohol also selectively inhibits motor activity in the upper airway with a corresponding increase in inspiratory resistance and snoring. Gabapentin and trazadone have shown some positive effects as sleep aids in patients with alcoholism. Trazadone has been the medication of choice to treat insomnia in early recovery for many years. Gabapentin is also relatively safe with few drug-drug interactions, low addictive potential, and no hepatic metabolism. It is known to increase cerebral concentrations of the inhibitory neurotransmitter GABA and is involved in the modulation of glutamate and norepinephrine. Rozarem can be of help by acting as an agonist at melatonin receptor and increasing total sleep time and decreasing sleep onset latency.

Marijuana with chronic use can lead to a reduction in stage N3 and decreased total sleep time. IT can also lead to decrease in REM percentage and prolongation or REM latency.

Nicotine causes longer sleep latency, decreased total sleep time, increased REM onset and decreased stage N3 sleep.

 

What to do if my hair is falling out from my medication?

Yes, it is possible with certain medications that it can accelerate hair loss and we always must evaluate the  risk vs. benefits of treatment in these cases. But there are some over the counter things that work if the causative medication has been helpful with psychiatric symptoms.  For starters, one can try 200mcgs of selenium in combination with 50 mg of zinc. Nioxin shampoo has also been recommended as well as addition of rosemary and lavender to hair products.  5000mcgs Biotin has also been recommended. It is  important to make sure  hair loss is not caused by another underlying medical condition like hypothyroidism or as a side effect from oral contraceptive pills. If you are loosing hair, discuss this with your doctor as there are treatments.