Ssri induced mania

Is Antidepressant-Induced Mania Possible?

Feeling invincible, impulsive, and endlessly energetic aren’t signs typically linked to depression — unless you may be experiencing antidepressant-induced mania linked to undiagnosed bipolar disorder.

Taking antidepressants may increase your chances of a manic episode in bipolar disorder but also in conditions that don’t typically feature the symptom — for example, major depressive disorder, if you have bipolar disorder that’s gone undiagnosed.

Not everyone taking antidepressants will experience mania.

Mania is a mood episode that presents with symptoms like agitation, elevated mood, and impulsivity. It’s primarily a formal symptom of bipolar disorder.

What are mania and hypomania?

Mania is a state of heightened mood, agitation, and intense physical and mental energy that can lead to major impairment in social or occupational areas of function. It can present in a number of ways, but often involves:

rapid speech
decreased need for sleep
feelings of grandiosity
racing thoughts
irritability
impulsivity
distractibility

Hypomania is a milder version of mania that involves some of the same symptoms but not to the point of causing significant impairment or keeping you from your everyday routine.

Antidepressants may increase the chances of an episode of mania or hypomania in certain people being treated for either unipolar or bipolar depression. That’s why some people say that antidepressants can make bipolar disorder worse. But it isn’t that simple.

While antidepressants are primarily prescribed for the treatment of major depressive disorder (unipolar or clinical depression), they may also be used to treat conditions featuring depressive episodes, like bipolar disorder.

In some cases, antidepressants are also used in the management of chronic pain, anxiety, and chronic insomnia.

Mania or affective switching?

During antidepressant treatment, shifting from an episode of depression to one that involves agitation is known as affective switching.

Some conditions, like bipolar disorder, are naturally characterized by cyclic affective switching. This means that people go through mood episodes in a given period of time. Antidepressant-induced mania isn’t part of the bipolar disorder cycle.

When you live with depression, you don’t go through mood episodes, like in bipolar disorder. Your mood typically stays the same, particularly in untreated depression. This is why mania during depression treatment can be the result of undiagnosed bipolar disorder.

But if you experience antidepressant-induced mania during your depression treatment, do you still have major depression or is it now bipolar disorder? Maybe neither.

Some experts argue that experiencing antidepressant-induced mania can’t be properly classified under current diagnostic criteria for depression or bipolar disorder and should have its own subtype category in the list of diagnoses.

Mania in bipolar disorder

Mania and hypomania are formal symptoms of bipolar disorder.

Mania is not a formal symptom of depression, a condition defined as persistent low mood and inability to experience joy.

You may go through depressive episodes when living with bipolar disorder, but it’s the presence of mania or hypomania that defines this condition.

You can experience bipolar disorder without depression, but you can’t experience bipolar disorder without mania or hypomania.

Who is more likely to experience antidepressant-induced mania?

People already living with bipolar disorder are more likely to experience a sudden episode of mania after taking certain antidepressants. But not everyone with the condition.

A 2018 review of bipolar depression notes that antidepressant-induced affective switching appears more common among people who:

experience depression with mixed features
are on older generation antidepressants
have a history of substance use disorder

You may be more likely to experience antidepressant-induced mania if you:

live with bipolar I disorder
are receiving antidepressant monotherapy
already experience rapid mood cycling

Women, younger people, and those with a family history of bipolar disorder, may have an increased chance of antidepressant-induced hypomania, according to a 2020 unipolar depression review.

Research suggests the use of older generation antidepressants, known as tricyclics, may cause a greater chance of mania compared to modern antidepressant options.

Tricyclic antidepressants include:

doxepin
imipramine
amitriptyline
clomipramine
desipramine
nortriptyline
amoxampine
protriptyline
trimipramine

Antidepressant-induced mania is not considered a common side effect of antidepressants.

According to cross-sectional patient data collected over a 2-year period, the challenges people may experience when taking these medications include:

indigestion
nausea
abdominal pain
diarrhea
constipation
sudden heat stroke
intense sweating
dry mouth
changes in sleeping patterns
diminished sex drive
changes in weight

Different antidepressants may come with side effects more common to their class.

Selective serotonin reuptake inhibitors (SSRIs), for example, are known to have common side effects of dizziness, anxiety, headaches, and restlessness.

There’s no scientific evidence suggesting antidepressants cause or trigger bipolar disorder.

Antidepressants may increase the chance you’ll experience an episode of mania if you have major depressive disorder when you also have bipolar disorder but haven’t yet received a diagnosis.

Experts have not reached a consensus on determining if this experience should lead to a new bipolar disorder diagnosis.

Currently, researchers are considering including a bipolar or depressive disorder subtype that may be specific to antidepressant sensitivity causing a manic episode.

If you’ve been diagnosed with major depressive disorder, experiencing mania is not typical. Any moods related to elation, agitation, or grandiosity may be medication-induced or could mean you also have bipolar disorder.

If you live with bipolar disorder, you can also experience antidepressant-induced mania outside of your cyclic mood cycles.

While antidepressant-induced mania remains diagnostically controversial, mood stabilizers may help prevent this type of affective switching, regardless of the underlying condition.

Article resources

Barbuti M, et al. (2017). Antidepressant-induced hypomania/mania in patients with major depression: Evidence from the BRIDGE-II-MIX study. https://www.sciencedirect.com/science/article/abs/pii/S0165032717300290
Beaupre M, et al. (2020). Antidepressant-associated mania in bipolar disorder: A review and meta-analysis of potential clinical and genetic risk factors. https://journals.lww.com/psychopharmacology/Abstract/2020/03000/Antidepressant_Associated_Mania_in_Bipolar.11.aspx
Bipolar disorder. (2020). https://www.nimh.nih.gov/health/topics/bipolar-disorder
Dailey MW, et al. (2022). Mania. https://www.ncbi.nlm.nih.gov/books/NBK493168/
Gill N, et al. (2020). A review of antidepressant-associated hypomania in those diagnosed with unipolar depression—risk factors, conceptual models, and management. https://www.researchgate.net/publication/340175853_A_Review_of_Antidepressant-Associated_Hypomania_in_Those_Diagnosed_with_Unipolar_Depression-Risk_Factors_Conceptual_Models_and_Management
Gitlin MJ. (2018). Antidepressants in bipolar depression: An enduring controversy. https://journalbipolardisorders.springeropen.com/articles/10.1186/s40345-018-0133-9
Patel R, et al. (2015). Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679886/
Ramic E, et al. (2020). Assessment of the antidepressant side effects occurrence in patients treated in primary care. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428926/
Table 2 list of antidepressants and their categorizations. (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK36406/table/ch2.t2/

Antidepressant-induced mania: an overview of current controversies

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Review

. 2003 Dec;5(6):407-20.

doi: 10.1046/j.1399-5618.2003.00067.x.

Joseph F Goldberg¹, Christine J Truman

Affiliations

Affiliation

¹ Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY 11004, USA. [email protected]

PMID: 14636364
DOI: 10.1046/j.1399-5618.2003.00067.x

Review

Joseph F Goldberg et al. Bipolar Disord. 2003 Dec.

. 2003 Dec;5(6):407-20.

doi: 10.1046/j.1399-5618.2003.00067.x.

Authors

Joseph F Goldberg¹, Christine J Truman

Affiliation

¹ Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY 11004, USA. [email protected]

PMID: 14636364
DOI: 10.1046/j.1399-5618.2003.00067.x

Abstract

Objective: The prevalence, characteristics, and possible risk factors associated with antidepressant-induced mania remain poorly described. The present review sought to identify published rates of antidepressant-induced mania and describe risk factors for its emergence.

Methods: A MedLine search was conducted of journals that focused on mania or hypomania associated with recent antidepressant use. Data from published reports were augmented with relevant findings from recent clinical trials presented at scientific conferences.

Results: Antidepressant-induced manias have been reported with all major antidepressant classes in a subgroup of about 20-40% of bipolar patients. Lithium may confer better protection against this outcome when compared with other standard mood stabilizers, although switch rates have been reported with comparable frequencies on or off mood stabilizers. Evidence across studies most consistently supports an elevated risk in patients with (i) previous antidepressant-induced manias, (ii) a bipolar family history, and (iii) exposure to multiple antidepressant trials.

Conclusion: About one-quarter to one-third of bipolar patients may be inherently susceptible to antidepressant-induced manias. Bipolar patients with a strong genetic loading for bipolar illness whose initial illness begins in adolescence or young adulthood may be especially at risk. Further efforts are needed to better identify high-vulnerability subgroups and differentiate illness-specific from medication-specific factors in mood destabilization.

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Typology, pathomorphosis and therapy of non-psychotic affective disorders in patients with epilepsy

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National Medical Research Center of Oncology. N.N. Blokhin

FIRST STAGE OF PROJECT COMPLETED SUCCESSFULLY

In September 2021, our Center won the competition of the Ministry of Science and Higher Education of the Russian Federation for the creation and development of a bioresource collection of cell lines and primary human tumors. For many years, the Center collected samples of tumors of different localizations, which were carefully and comprehensively studied in order to choose the best way to treat the patients of the Center. The collected tumor samples helped the Center's scientists develop new treatment tactics and test new drugs. In some cases, it was possible to preserve the viability of cells from tumor samples and create experimental models during long-term cultivation of tumor cells in nutrient media or transplantation into laboratory mice.

As a result, thousands of samples were dispersed among various institutes and laboratories of the Center, there was no unified register of samples, and information about them was distributed according to the principle of word of mouth. This situation did not contribute to the development of scientific research, it was necessary to create a single register of all biological samples of the center, a single information resource and a center for collective use. The Ministry of Higher Education and Science of the Russian Federation supported the scientists of the Center in this endeavor, and on September 28, 2021, Agreement No. 075-15-2021-1060 was signed between the Ministry and the Center on the implementation of the project "Creation and development of a bioresource collection of cell lines and primary human tumors" under the leadership of the Director of the Research Institute of Experimental Diagnostics and Therapy of Tumors Vyacheslav Stanislavovich Kosorukov.

In the 3 months that have passed since the beginning of the project, a new laboratory "Bioresource Collection of Cell Lines and Primary Tumors" was created at the Center, for which premises were allocated on the basis of the Research Institute of EDiTO and equipment was purchased: laminar cabinets for working with samples in sterile conditions, SO ₂ - incubators for cultivating cell lines, cryostorage, as well as other devices and consumables. To form the scientific team of the new laboratory, an open competition was announced for filling the positions of researchers and director.

The creation of a laboratory is just one of the stages in solving the main task of this project: to make samples of the collection, as well as information about them, available to domestic and foreign scientists, to establish mechanisms for the functioning of the collection and its replenishment. First of all, it was necessary to carry out an inventory of all the samples available in various departments of the Center, which was successfully completed. In total, 10,664 samples of cell lines and hybridoma clones, 1,787 samples of transplanted tumor strains, and 2,466 samples of primary tumors and tissues were included in the registry. During the implementation of the first stage of the project, 1653 more samples (storage units) of cell lines and hybridoma clones and more than a hundred units of samples of transplanted strains and tumors were added to this number. For each sample of the Collection there is information about its characteristics, which is constantly supplemented, and this forms a large array of changing data. To use these data, a special information resource is required, and the development of such a resource was started from the first days of the project.

An important component of the functioning of the collection is the analysis of the quality of samples, as well as the study of their genetic and phenotypic characteristics. At the first stage of the project, standards for the characterization of adhesive and suspension cell lines, hybridoma clones and monoclonal antibodies were developed, and corresponding methodologies were prepared.

The first assessments of the quality of the samples showed that most of them are well preserved, despite the long periods of preservation: most of the cell lines and transplanted tumor strains have shown their viability and the absence of microbiological contamination. In total, more than a hundred samples were examined and 134 tests were carried out for contamination with mycoplasma 29cell lines from commercial sources, 16 cell cultures obtained at the N. N. N.N. Blokhin” of the Ministry of Health of Russia, 17 transplantable tumor strains and 37 hybridoma clones. For hybridoma clones, their productivity and stability were additionally evaluated.

33 cell lines with the best quality indicators were selected to form the first lots of the collection - 50 samples (cryotubes) of each line of one passage. At the second stage of the project, the biological material of these lots will be characterized by genetic and immunochemical methods in accordance with the developed methodologies. To do this, it will be enough to unfreeze one or two cryovials from each lot, and as a result, get a complete and accurate picture of the properties of the remaining samples of the lot, which will be provided for research within the framework of the shared use center being created. Lots of characterized samples will be formed according to the same principle in the future.

Transplanted tumor strains and clinical samples of tumors are a valuable resource for many scientific studies, but their production and standardization are associated with a number of objective difficulties. Unlike cell lines, which can be generated and frozen in a few tens or hundreds of tubes, and then analyzed according to specific tasks, clinical samples require some preparation immediately after the collection of the material, and this preparation depends on the design of the experiment in which it will be used. sample. In an attempt to predict the future use of clinical samples, we applied several preparation options for each tumor sample. Samples for genetic analysis were isolated from the tumor tissue of each patient, cell and tissue lysates, cell suspensions were obtained, and paraffin blocks were made to perform immunochemical methods. Thus, samples from 15 primary tumors of various localizations were prepared and deposited: skin melanoma, uveal melanoma, ovarian cancer, liver cancer, rectal cancer, chorionepithelioma, gastrointestinal stromal tumor, as well as tumor samples of 10 transplantable strains obtained from malignant neoplasms of the cervix, body of the uterus, prostate, bladder, liver, colon and chorionepithelioma. For transplanted strains of human tumors, the tumorigenicity of tumor cells was confirmed in experiments on athymic mice. Samples of these tumors were prepared for further study by genetic and immunochemical methods at the second stage of the project.

Cell lines and tumor samples as a research tool have their advantages and limitations. Cell lines are adapted to growth outside the body, so the processes occurring in them can be observed in vitro, but the two-dimensional nature of their growth does not fully reproduce all the features of the functioning of cells in the body. Transplanted tumor strains and tumor samples have a three-dimensional structure, therefore, they reproduce body tissues better, but the study of the processes occurring in them is limited by the impossibility of culturing them. The co-executor of this project is the Research Institute of Human Morphology named after academician Avtsyn, where methods have been developed for obtaining three-dimensional cell lines (tumoroids or spheroids), a kind of compromise version of a model system for studying tumor processes and the action of various kinds of substances.

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