The higher the dose of Abilify, the more chance of unwanted side effects.
It's mechanism of action is different from those of the other FDA-approved atypical. Usually for anxiety and depression, the dose is very low around 1- 2.5mg with 5 mg max out. Where as for other conditions like schizophrenia and bipolar the amount climbs up to 20-30mg, a big difference.
It is a partial DA2 agonist, that mediates DA release to about 30-20%. Which almost puts close to the antagonist category but is still not a antagonist obviously. It is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics displays an antagonist profile at the 5-HT2A receptor. It also antagonizes the 5-HT7 receptor and acts as a partial agonist at the 5-HT2C receptor, both with high affinity. The latter action may underlie the minimal weight gain seen in the course of therapy.
Most atypical antipsychotics bind preferentially to extrastriatal receptors (outside the corpus striatum), but aripiprazole appears to be less preferential in this regard, as binding rates are high throughout the brain.It implicates 5-HT7 antagonist as playing a major role in aripiprazole antidepressant effects, similarly to amisulpride, another AAP.
The half-life is long at approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days.
An important fact is Aripiprazole is a substrate of CYP2D6 and CYP3A4. So, Coadministration with medications that inhibit (e.g. paroxetine, fluoxetine) or induce these metabolic enzymes are known to increase and decrease, respectively, plasma levels of aripiprazole. So, anyone taking aripiprazole should be aware that their dosage of aripiprazole may need to be decreased.
Below are some studies and papers concerning aripiprazole. I may have to make two posts out of it:
It is one of the atypicals with fewest side effects. It's dose a can be varied depending on the mental disorder with depression and anxiety being on the low end. It's mechanism of action should really make it a third generation anti-psychotic.
It is a DA2 partial agonist. So, basically it is a dopamine mediator and stabilizer
They use it's scientific name in the graph, aripiprazole. It's easy to see how Abilify levels it out. While other antipsychotics fluctuate.
This is from a CNS paper:
Aripiprazole, an effective SGA for the treatment of schizophrenia, has a unique pharmacologic profile in that it functions through partial agonism at D2/3 receptors.1 Aripiprazole does not induce extrapyramidal symptoms, an increase in prolactin, weight gain, type II diabetes, or sedation. Instead of blocking D2/3 receptors as is the case with other antipsychotics, aripiprazole acts as a partial agonist at dopamine receptors. In vitro assay shows aripiprazole to be less potent as a receptor agonist than dopamine (range 30% to 80. In behavioral tests, aripiprazole blocks apomorphine-induced climbing behavior (mediated by dopamine receptors) at low dose without inducing catalepsy, unlike typical antipsychotics which do produce catalepsy. This suggests that aripiprazole’s primary mechanism of action of partial agonism at D2/3 receptors has successfully differentiated antipsychotic efficacy and the adverse effects associated with typical antipsychotics.
Aripiprazole is a partial agonist of 5-HT1A receptors at therapeutic concentrations as well. Clozapine and the SGAs ziprasidone and quetiapine also exhibit 5-HT1A partial agonism at clinically effective doses. This distinguishes aripiprazole and these other atypical antipsychotics from first-generation antipsychotics, and suggests they may have particular utility in ameliorating the affective components of psychosis, such as anxiety and negative symptoms of schizophrenia. It appears that the distinctive therapeutic profiles of SGAs are related to partial agonist at dopamine and serotonin receptors.
5HT1a agonists have been used to treat depression and anxiety.
This from Wiki:
Quote:
Some of the atypical antipsychotics like aripiprazole[21] are also partial agonists at the 5-HT1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs).[
5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus, and may be useful for improving the symptoms of schizophrenia and Parkinson's disease.[33][34] As mentioned above, some of the atypical antipsychotics are 5-HT1A receptor partial agonists, and this property has been shown to enhance their clinical efficacy.[33][35][36] Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects seen upon postsynaptic activation of the 5-HT1A receptor.[37][38]
5-HT1A receptor - Wikipedia, the free encyclopedia
Here is a very short and succient article by a pdoc:
abilify | Search Results | Thought Broadcast
Quote:
So, Abilify is a potent antagonist at the dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors, a moderate one at dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors, and even does a little serotonin reuptake inhibition.
Like Seroquel, Geodon, and Clozaril (clozapine), Abilify is a partial agonist at serotonin 5-HT1A receptors, but what makes it special (for now) is also being a partial agonist at the dopamine D2 receptors. Blocking 5-HT2A, and having a positive effect on 5-HT1A and D2 are responsible for fewer movement disorder and prolactin problems, and all those agitating/antsy/activating side effects.
Abilify (aripiprazole) Overview | The Good, the Bad & the Funny of these Crazy Meds
Here is Crazy Meds. 2 part paper with plenty of links and their down to earth writing style If you want to see studies and/or do research. This is it!
Finding the Treatment Options that Suck Less | The Good, the Bad & the Funny of these Crazy Meds
Finding the Treatment Options that Suck Less | The Good, the Bad & the Funny of these Crazy Meds
This is a long research paper by CANMAT abot medication stratigies for anxixiety and co-morbid disorders, publishes in 2012.
https://www.aacp.com/pdf%2F0212%2F0212ACP_Schaffer.pdf
Quote:
Mechanisms of Action
Aripiprazole is what is known as a partial agonist (stimulator) of dopamine D1, D2, and D3 receptors, in contrast to all other typical and atypical antipsychotics, which are full antagonists (blockers) of dopamine receptors. The partial agonism means that when aripiprazole binds to the receptor, it activates the receptor only about 20%, but never any more, no matter how high the dose or blood levels of the drug are.
Since aripiprazole “sits” on the receptor, any degree of excess dopamine that may occur in mania or schizophrenia cannot reach these dopamine receptors, so aripiprazole effectively produces an 80% functional blockade. The 20% stimulation (agonism) of dopamine D2 receptors is sufficient to make aripiprazole the only typical or atypical antipsychotic that significantly lowers prolactin levels. Aripiprazole is also a partial agonist at serotonin 5HT1A receptors, like the drug buspirone (Buspar), which is known for its antidepressant and antianxiety effects. Aripiprazole is a full blocker of 5HT2A receptors, which might also contribute to its antidepressant effects, and (like the antidepressant Trazodone) its ability to increases the deeper phases of sleep known as slow wave sleep.
Aripiprazole (Abilify), the Atypical Atypical Antipsychotic : Bipolar Network News
Here is a study Abilify + Zoloft with positive results. It seems like a tolerable SSRI with Abilify's partial DA2 agonism and it's 5HT actions can possibly be a very good combo. Note in the study the experimental group was only on 2.5mg Abilify.
Quote:
Adjunctive low-dose aripiprazole with standard-dose sertraline in treating fresh major depressive disorder: a randomized, double-blind, controlled study.
Lin CH, Lin SH, Jang FL.
Source
Department of Psychiatry, Chi-Mei Medical Center, Tainan City, Taiwan.
Abstract:
OBJECTIVES:
Second-generation (atypical) antipsychotics have been accepted as an adjunctive medication in patients with treatment-resistant depression. This clinical trial evaluated the efficacy and safety of low-dose aripiprazole combined with regular-dose sertraline for acute major depressive episode in non-treatment-resistant depression outpatients.
METHODS:
The study patients were 18- to 65-year-old outpatients fulfilling the criteria of major depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The patients were randomly assigned to 2 groups: one with sertraline 50 mg/d plus aripiprazole 2.5 mg/d and the other with sertraline 50 mg/d plus placebo. After baseline assessment, the subjects were followed up at weeks 1, 2, 4, 6, and 10. The primary efficacy was the score change of the 17-item Hamilton Rating Scale for Depression (HAM-D17), and secondary efficacies were the score of Short Form 36 Health Survey, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. This study also monitored patients for movement disorder using Simpson-Angus Scale and Barnes Akathisia Rating Scale.
RESULTS:
Twenty-one patients were assigned to the aripiprazole group and 20 to the placebo group. Because of high dropout rate, only data of the first 4 weeks were analyzed. The aripiprazole group exhibited significantly better efficacy than the placebo group in mean total score changes of HAM-D17 from the baseline to weeks 1, 2, and 4. The item "work and social activities" of HAM-D17 showed significant improvement at week 2, and the item "somatic symptoms (GI)" showed significant improvement at week 1. The aripiprazole group exhibited significant improvement in "social role function" section of Short Form 36 Health Survey at week 4. The mean total score of Clinical Global Impressions-Severity showed marginally significant improvement in the aripiprazole group. In Clinical Global Impressions-Improvement, patients in the aripiprazole group had scores of less than 2 (much improved) at weeks 2 and 4, and the scores of the placebo group were greater than 2.4 (indicating a minimal improvement). No patients had akathisia during the trial period.
CONCLUSIONS:
The primitive data showed that adjunctive low-dose aripiprazole could augment the efficacy of regular-dose sertraline in fresh major depressive disorder. A large-scale study is needed to confirm this finding.
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Another study that shows Abilify's therapeutic effects for depression and anxiety!
Quote:
J Clin Psychiatry. 2008 Dec;69(12):1928-36. Epub 2008 Dec 2.
Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features.
Trivedi MH, Thase ME, Fava M, Nelson CJ, Yang H, Qi Y, Tran QV, Pikalov A, Carlson BX, Marcus RN, Berman RM.
Source
UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9119, USA. Madhukar.Trivedi@UTSouthwestern.edu
Abstract
OBJECTIVE:
To evaluate the efficacy of adjunctive aripiprazole to standard antidepressant therapy (ADT) for patients with DSM-IV major depressive disorder with anxious/atypical features at baseline.
METHOD:
Data from 2 identical 14-week studies (an 8-week prospective ADT treatment phase and a 6-week randomized, double-blind phase) of aripiprazole augmentation were pooled to evaluate efficacy and safety in the 2 subgroups. The primary efficacy endpoint was mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from end of ADT treatment to end of randomized treatment (last observation carried forward). Anxious depression was defined by a Hamilton Rating Scale for Depression anxiety/somatization factor score ≥ 7, and atypical depression was defined by previously described criteria on the Inventory of Depressive Symptomatology-Self-Report. Both anxious and atypical subtypes were defined based on symptoms at entry into prospective ADT (week 0). Patients were enrolled between June 2004 and April 2006 in one study and from September 2004 to December 2006 in the other (total randomized population, N = 742; anxious/nonanxious population, N = 740; atypical/nonatypical population, N = 737).
RESULTS:
Completion rates were between 84% and 90% and comparable across all subgroups, with low discontinuations due to adverse events. Patients receiving adjunctive aripiprazole demonstrated significantly greater improvement in MADRS total score versus patients receiving adjunctive placebo, starting at week 1 or week 2 and continuing through to endpoint (anxious: -8.72 vs. -6.17, p ≤ .001; nonanxious: -8.61 vs. -4.97, p ≤ .001; atypical: -9.31 vs. -5.15, p ≤ .001; nonatypical: -8.08 vs. -6.22, p < .05). At endpoint, remission rates were also significantly higher with adjunctive aripiprazole versus adjunctive placebo (p < .05) in all subgroups. Treatment emergent adverse event profile was similar in all subgroups and comparable to the total population. Reporting of akathisia and weight gain on aripiprazole treatment did not differ between subgroups.
CONCLUSION:
Adjunctive aripiprazole is an effective treatment for patients with major depression presenting with either anxious or atypical features.
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From another source:
"There are D2 receptors in the pancreas which usually mediate inhibition of insulin secretion, atypical antipsychotics can mess with these and that's thought to be atleast one reason why blood sugar levels go up and so on.
Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion
GLUT5 expression may also play a role (atleast in Zyprexas case):
Zyprexa's Weight Gain: Does What You Eat Matter More Than How Much?
In this case Zyprexa is thought to make your body use fat, not carbs, as fuel, however this was less the case with abilify and others:
In the fed state, Zyprexa and Clozaril do a massive conversion to fat utilization, Risperdal a medium, and sulpiride minimal conversion. Geodon has a lesser effect than Zyprexa, and appears to normalize; Abilify and Haldol seem close to normal."
http://thelastpsychiatrist.com/2010/...a_and_fat.html
*Here is a chart on the likelihood of side-effects. Charts, you can never have to many charts!!!;D
Antipsychotics: relative adverse effects – a rough guide
This is from a very informative CNS paper, the link below:
Quote:
Aripiprazole, an effective SGA for the treatment of schizophrenia, has a unique pharmacologic profile in that it functions through partial agonism at D2/3 receptors.1 Aripiprazole does not induce extrapyramidal symptoms, an increase in prolactin, weight gain, type II diabetes, or sedation. Instead of blocking D2/3receptors as is the case with other antipsychotics, aripiprazole acts as a partial agonist at dopamine receptors. In vitro assay shows aripiprazole to be less potent as a receptor agonist than dopamine (range 30% to 80. In behavioral tests, aripiprazole blocks apomorphine-induced climbing behavior (mediated by dopamine receptors) at low dose without inducing catalepsy, unlike typical antipsychotics which do produce catalepsy. This suggests that aripiprazole’s primary mechanism of action of partial agonism at D2/3 receptors has successfully differentiated antipsychotic efficacy and the adverse effects associated with typical antipsychotics.
Aripiprazole is a partial agonist of 5-HT1A receptors at therapeutic concentrations as well. Clozapine and the SGAs ziprasidone and quetiapine also exhibit 5-HT1A partial agonism at clinically effective doses. This distinguishes aripiprazole and these other atypical antipsychotics from first-generation antipsychotics, and suggests they may have particular utility in ameliorating the affective components of psychosis, such as anxiety and negative symptoms of schizophrenia. It appears that the distinctive therapeutic profiles of SGAs are related to partial agonist at dopamine and serotonin receptors.
http://www.primarypsychiatry.com/asp...articleid=1149
5HT1a agonists have been used to treat depression and anxiety.
This from Wiki:
Quote:
Some of the atypical antipsychotics like aripiprazole[21] are also partial agonists at the 5-HT1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs).[
5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus, and may be useful for improving the symptoms of schizophrenia and Parkinson's disease.[33][34] As mentioned above, some of the atypical antipsychotics are 5-HT1A receptor partial agonists, and this property has been shown to enhance their clinical efficacy.[33][35][36] Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects seen upon postsynaptic activation of the 5-HT1A receptor.[37][38]
5-HT1A receptor - Wikipedia, the free encyclopedia
Here is a very short and succinct article by a pdoc:
abilify | Search Results | Thought Broadcast
Quote:
So, Abilify is a potent antagonist at the dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors, a moderate one at dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors, and even does a little serotonin reuptake inhibition.
Like Seroquel, Geodon, and Clozaril (clozapine), Abilify is a partial agonist at serotonin 5-HT1A receptors, but what makes it special (for now) is also being a partial agonist at the dopamine D2 receptors. Blocking 5-HT2A, and having a positive effect on 5-HT1A and D2 are responsible for fewer movement disorder and prolactin problems, and all those agitating/antsy/activating side effects.
Abilify (aripiprazole) Overview | The Good, the Bad & the Funny of these Crazy Meds
Here is Crazy Meds. 2 part paper with plenty of links and their down to earth writing style If you want to see studies and/or do research. This is it!
Finding the Treatment Options that Suck Less | The Good, the Bad & the Funny of these Crazy Meds
Finding the Treatment Options that Suck Less | The Good, the Bad & the Funny of these Crazy Meds
This is a long research paper by CANMAT about medication strategies for anxiety and co-morbid disorders, publishes in 2012.
https://www.aacp.com/pdf%2F0212%2F0212ACP_Schaffer.pdf
Quote:
Mechanisms of Action
Aripiprazole is what is known as a partial agonist (stimulator) of dopamine D1, D2, and D3 receptors, in contrast to all other typical and atypical antipsychotics, which are full antagonists (blockers) of dopamine receptors. The partial agonism means that when aripiprazole binds to the receptor, it activates the receptor only about 20%, but never any more, no matter how high the dose or blood levels of the drug are.
Since aripiprazole “sits” on the receptor, any degree of excess dopamine that may occur in mania or schizophrenia cannot reach these dopamine receptors, so aripiprazole effectively produces an 80% functional blockade. The 20% stimulation (agonism) of dopamine D2 receptors is sufficient to make aripiprazole the only typical or atypical antipsychotic that significantly lowers prolactin levels. Aripiprazole is also a partial agonist at serotonin 5HT1A receptors, like the drug buspirone (Buspar), which is known for its antidepressant and antianxiety effects. Aripiprazole is a full blocker of 5HT2A receptors, which might also contribute to its antidepressant effects, and (like the antidepressant Trazodone) its ability to increases the deeper phases of sleep known as slow wave sleep.
For reference of potential side effects:
http://www.npc.nhs.uk/therapeutics/c...izophrenia.pdf
Extrapyramidal symptoms: Movement related symptoms including akathisia (inner restlessness), dystonia (muscle tension/contractions), Dyskinesias (rapid blinking), Pseudoparkinsonism: (cogwheel rigidity, resting tremor).
Anticholinergic side effects: Dry mouth, constipation, urinary hesitancy.
Hypotension: Dizziness, low blood pressure, sinus congestion.
Prolactin Elevation: Raised amount of the hormone Prolactin (also know as Hyperprolactinaemia), side effects associated with this state can include sexual dysfunction, weight gain and secretion of breast milk.
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