Early Intervention Improves Outcomes in Early-Stage Schizophrenia

 

doctor with teen boy

A recent meta-analysis of 10 studies found that early intervention after a first episode of psychosis or in the early stages of a schizophrenia spectrum disorder led to better patient outcomes than treatment as usual.
The meta-analysis by researcher Christoph U. Correll and colleagues appeared in the journal JAMA Psychiatry in 2018. The 10 studies that were included had randomized a total of 2,176 patients to receive either treatment as usual or early intervention services, which typically include efforts at early detection of symptoms, early treatment with low doses of antipsychotic medication, interventions to prevent relapse, and strategies to help patients return to normal work and social activities.

Those patients who received early intervention services were less likely to discontinue treatment, were less likely to have a psychiatric hospitalization, were more involved in school or work, and had less severe symptoms, including both positive and negative symptoms of schizophrenia.

The authors called for better funding and implementation of early intervention services in early psychosis or the beginning stages of schizophrenia.

Editor’s Note: This finding with regard to schizophrenia spectrum disorders emphasizes the enormous disparity in allocation of research resources for the study of early psychosis versus early bipolar disorder, where almost no studies of this kind have been done.

The mean age of the patients in this psychosis meta-analysis was 27.5 years. Symptoms of bipolar disorder can often begin earlier, in childhood, and early onset of bipolar disorder predicts poor long-term outcomes into adulthood and is associated with a high risk of substance abuse and suicide. This editor (Robert M. Post) and many colleagues have witnessed two decades of scientific literature on early-onset bipolar disorder. We know that early intervention is necessary, but more treatment studies are needed at the early stages of the illness, and calls for funding treatment-focused research have gone unheeded.

More advocacy is needed among families affected by bipolar disorder and advocacy groups interested in better treatment of bipolar disorder. We must try to change the abysmal status quo and campaign publicly, privately, and politically for more funds and public health attention to be directed toward early intervention in bipolar disorder.

Hearing Aids May Lessen Cognitive Decline, Memory Loss

July 11, 2018 · Posted in Current Treatments · Comment 

hearing aid

A 2018 article by researcher Asri Maharani and colleagues in the Journal of the American Geriatrics Society reports that using a hearing aid was associated with better scores on a test of episodic memory, and that declines in episodic memory slowed after participants began using hearing aids.

The study included 2,040 adults aged 50 years and up. Maharani and colleagues used data from the Health and Retirement Study, which measured participants’ cognitive functioning every two years for 18 years. Participants were asked to recall 10 words both immediately and after some delay.

The authors suggested that improving access to hearing aids earlier in the course of hearing impairment might help to stem the rise of dementia.

Meta-Analysis Finds Antidepressants More Effective Than Placebo

July 3, 2018 · Posted in Current Treatments · Comment 

antidepressants

In a 2018 article in the journal The Lancet, researchers led by Andrea Cipriani compared the efficacy of 21 different antidepressants and established that antidepressants are more effective than placebo at reducing unipolar depression. To date, this is the largest meta-analysis of double-blind, randomized controlled studies of antidepressant efficacy, including 522 trials and a total of 116,477 participants. All 21 of the antidepressants were found to be more effective than placebo.

Looking at head to head studies, Cipriani and colleagues found that the most effective antidepressants were agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine. The least effective antidepressants were fluoxetine, fluvoxamine, reboxetine, and trazodone.

In terms of tolerability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were most tolerable to patients, while amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine caused the most study dropouts due to side effects. Only agomelatine and fluoxetine had better dropout rates than placebo.

Interestingly, agomelatine, the medication found to be most effective and most tolerable, is unavailable in the US. Pharmaceutical company Novartis, which owns the rights to the drug, was disappointed by some lackluster studies of the drug and never applied for Food and Drug Administration approval to sell it in the US. The studies found potential problems regarding drug interactions related to the metabolic enzyme CYP1A2 and a risk of liver damage with longer-term use.

Editor’s Note: This meta-analysis should end any remaining controversy about the efficacy of antidepressants in the acute treatment of unipolar depression.

This study did not address maintenance treatment for the prevention of depressive episodes. Researcher John R. Geddes and colleagues have found robust, statistically significant data that continuation treatment with antidepressants can prevent depressive relapse, suggesting that if patients continue taking effective antidepressants, rather than switching to placebo, the antidepressants can reduce depressive occurrences by about 70%.

It is now recommended in most guidelines that patients with two or three prior episodes of depression consider staying on antidepressants indefinitely over their lifetime in order to prevent recurrence. Antidepressants increase the creation of new neurons and brain-derived neurotrophic factor (BDNF), which protects neurons and is important for learning and memory. Antidepressants can also prevent loss of hippocampal volume.

Large Finnish Study Finds Lithium is Best at Preventing Re-Hospitalizations in Bipolar Disorder

June 13, 2018 · Posted in Current Treatments, Peer-Reviewed Published Data · Comment 

hospital

A 2018 article in the journal JAMA Psychiatry reports that lithium and long-acting antipsychotic injections were most effective at preventing re-hospitalizations among people with bipolar disorder.

The study by Markku Lähteenvuo and colleagues included 18,018 Finnish patients with bipolar disorder. A national database contained information on any hospitalizations that occurred among the patients and what medications were dispersed to patients.

Among the participants, 54% (9,721 patients) were re-hospitalized at least once over a study period of 16 years. Medications associated with the smallest risk of re-hospitalization for psychiatric reasons were long-acting injections of risperidone, gabapentin, long-acting injections of perphenazine, and lithium carbonate.
When the researchers looked at hospitalizations for any cause (not just psychiatric illness), lithium was associated with the least risk of re-hospitalization, while benzodiazepines had the greatest risk, both for psychiatric re-hospitalization and re-hospitalization for any cause.

Long-acting injectable medications were associated with less risk of re-hospitalization compared to the identical medications delivered orally.

Lähteenvuo and colleagues concluded, “Lithium…should remain as the first line of treatment for bipolar disorder, after decades of underprescription.” They suggest that long-acting injectable medications may be a good alternative to prevent relapse in patients for whom lithium is unsuitable.

Editor’s Note: In addition to lithium’s ability to prevent depressions and manias, it also increases the volume of the hippocampus and protects against a diagnosis of dementia in old age. Lithium decreases the risk for suicide and also increases the length of telomeres, bits on the ends of DNA strands that protect them as they replicate, which are important to the maintenance of both physical and psychiatric health. When lithium is used cautiously to maintain doses below a given patient’s side effects threshold, it is very well tolerated by most individuals.

Third Study Suggests Cariprazine Is Effective in Bipolar Depression

June 2, 2018 · Posted in Current Treatments, Potential Treatments · Comment 

cariprazine

The atypical antipsychotic drug cariprazine (sold under the name Vraylar in the US) is currently approved by the US Food and Drug Administration for the treatment of schizophrenia and manic or mixed episodes of bipolar disorder. Based on recent successful phase 3 trials in bipolar depression, the pharmaceutical companies that produce cariprazine, Allergan and Gedeon Richter, plan to apply for a change in FDA labeling later this year to reflect the drug’s apparent ability to treat bipolar depression as well.

While many drugs can prevent or treat mania, treating bipolar depression has typically been more of a challenge. The most recent 6-week trial of cariprazine in 493 patients showed that a dose 1.5mg/day was significantly more effective than placebo at reducing depression ratings. (A dose of 3mg/day did not show superiority over placebo as it had in previous trials of cariprazine.)

Side effects reported in the trial were mild and included restless legs, nausea, and fatigue. Five percent of those who received cariprazine discontinued the drug due to side effects, compared to three percent of those who received placebo.

The mechanism by which cariprazine improves depression is not yet clear. The drug is a dopamine partial agonist, but unlike aripiprazole (Abilify) and brexpiprazole (Rexulti), which have more potent effects on D2 receptors than on D3 receptors, cariprazine is more potent at dopamine D3 receptors. Whether this difference accounts for the positive effects in bipolar depression that aripiprazole and brexpiprazole do not have remains to be seen.

Psychoeducation Is a Must for Bipolar Disorder

May 28, 2018 · Posted in Current Treatments · Comment 

group psychoeducation

In 2018, researcher S.A. Soo and colleagues published a systematic review in the Journal of Clinical Psychiatry that analyzed findings from 40 randomized studies of psychoeducation for the management of bipolar disorder and compared the results for different types of psychoeducation: group, family, individual, and internet-based. Most of the randomized controlled trials (28 of 40 studies, 70.0%) assessed group or family psychoeducation, which had many benefits, while studies of individual or internet-based psychoeducation tended to be inconsistent.

The findings: “Group psychoeducation was associated with reduced illness recurrences, decreased number and duration of hospitalizations, increased time to illness relapse, better treatment adherence, higher therapeutic lithium levels, and reduced stigma. Family psychoeducation was associated with reductions in illness recurrence, hospitalization rates, and better illness trajectory as well as increased caregiver knowledge, skills, support, and sense of well-being and reduced caregiver burden.”

Editor’s Note: Given these results, it appears that group or family psychoeducation is a critical component to good care. Soo and colleagues suggest that future studies should directly compare different types of psychoeducation to each other to evaluate whether specific benefits are useful at various stages of illness.

Vortioxetine Improves Processing Speed in Depression

May 23, 2018 · Posted in Current Treatments · Comment 

TrintellixIn May 2018, the US Food and Drug Administration (FDA) approved a label change for the antidepressant vortioxetine (Trintellix), reflecting new data that show the drug can improve processing speed, an aspect of cognitive function that is often impaired in people with depression. Vortioxetine was first approved by the FDA for the treatment of depression in 2013.

The approval followed eight-week double-blind placebo-controlled studies of vortioxetine’s effects on cognitive function in adults aged 18–65 who have depression. The studies were known as FOCUS and CONNECT. Patients received either 10mg/day, 20mg/day, or placebo. Those who took vortioxetine showed improvement on the Digit Symbol Substitution Test, a measure of processing speed, in addition to improvement in their depression.

Editor’s Note: This is the first time the FDA has approved labeling that describes an antidepressant as improving aspects of cognition in depression. Cognition is impaired in many patients with depression, such that this component of the drug’s effects could be of clinical importance. Among the 5 serotonin (5HT) receptor effects of the drug (in addition to the traditional blockade of serotonin reuptake shared by all selective serotonin reuptake inhibitor antidepressants (SSRIs)), it is likely that vortioxetine’s effects in blocking 5HT-3 and 5HT-7 receptors are important to the drug’s effects on processing speed.

The Gold Standard in Bipolar Disorder Treatment

May 21, 2018 · Posted in Current Treatments · Comment 

Last year our Editor-in-Chief Robert M. Post participated in a symposium at the annual meeting of the American Psychiatric Association on the best treatments for bipolar disorder. An article in Psychology Today describes some of the conclusions of the expert panel.

FDA Approves Lurasidone for Bipolar Depression in Children and Adolescents

April 16, 2018 · Posted in Current Treatments · Comment 

In March 2018, the US Food and Drug Administration approved the antipsychotic drug lurasidone (Latuda) for the treatment of bipolar depression in children and adolescents aged 10–17 years. Lurasidone was already approved for adults with bipolar depression, as an add-on treatment to the mood stabilizers lithium and valproate, and for schizophrenia in people aged 13 years and up.

A 6-week clinical trial in 347 youth compared lurasidone (in doses ranging from 20 to 80 mg/day) to placebo and found that those who received lurasidone showed significant improvements in depression compared to those who received placebo. The average dose was below 40 mg/day. The research by Melissa P. DelBello and colleagues was published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2017.

In the study, lurasidone was well-tolerated. Side effects included nausea, sleepiness, minimal weight gain, and insomnia. Lurasidone did not seem to affect glucose, triglycerides, cholesterol, or blood pressure.

Editor’s Note: This is the first drug to be approved for bipolar depression in this age range. This editor (Robert M. Post) has written extensively on the high incidence of childhood onset bipolar disorder in the US, and especially in the offspring of parents with bipolar disorder.
It is important to be alert to the possibilities of depression and bipolar disorder in children in the US (along with related illnesses such as anxiety, oppositional defiant disorder, and attention deficit hyperactivity disorder (ADHD)), as early-onset illness tends to have a more severe long-term course than adult-onset depression and bipolar disorder. A longer delay between the emergence of symptoms and the first treatment for bipolar disorder is also a risk factor for more severe depression, more time depressed, and a poorer outcome in adulthood.

Parents of children aged 2-12 who have mood or behavioral problems are encouraged to consider joining the Child Network at our website, bipolarnews.org (click on the tab for the Child Network). By participating in this research network, parents are able to make a weekly rating of the severity of their children’s symptoms of anxiety, depression, ADHD, oppositional behavior, and mania via the secure website. The ratings can then be shared with the child’s clinicians for easy visualization of the course of symptoms over time, which may help with treatment decisions.

Using Antidepressants During Pregnancy Likely Does Not Increase Autism Risk

March 14, 2018 · Posted in Current Treatments · Comment 

antidepressants during pregnancy

In the past year or so, several meta-analyses have analyzed data from numerous studies of a possible link between antidepressant use in pregnancy and autism in the offspring. In a 2017 article in the Journal of Clinical Psychiatry, researcher Chittaranjan Andrade offers a meta-analysis of these previous meta-analyses, and determines that while there is a small link between antidepressant use in pregnancy and autism in the offspring, it is most likely the mother’s depressive illness rather than the medications that is responsible for this link.

Andrade found that antidepressant exposure was linked to an increased risk of autism spectrum disorders in the offspring even when the antidepressant use occurred only before conception occurred, when it could not possibly have affected the future fetus’ physiology. This implies that it is the mother’s illness rather than the antidepressant treatment that is a determinant of autism risk.

Next Page »