Medications for bipolar disorder: antidepressants and the risk of manic phases

By Cristiano Antonino On Mar 30, 2023

How is it treated and what are the medications for bipolar disorder? Pharmacological therapy with antidepressants and that associated with mood stabilizers: a research analyzes the risk of inducing the manic phase in the treatment of bipolar depression

What does it mean to be bipolar?

Bipolar disorders are a set of pathologies characterized by the alternation of:

depressive phases: characterized by depressed mood, markedly decreased interest and ability to experience pleasure, decreased self-esteem, feelings of guilt, psychomotor agitation or retardation, insomnia or hypersomnia, decreased appetite, asthenia, decreased libido, decreased the ability to think and concentrate, recurring thoughts of death etc.;
phases of manic excitement: characterized, instead, by euphoria or irritability, tendency to accelerate thinking and speaking, decreased need for sleep, distractibility, excessive involvement in playful activities that have a high potential for harmful consequences, increased goal-directed activities social, work, sexual.

The phases are interspersed with intercritical periods free of symptoms or with attenuated symptoms and follow one another according to variable configurations in the different individuals affected by the disorder.

In a significant percentage of patients with bipolar disorder (30-40%) there is also at least one personality disorder that influences the patient’s behavior and experiences in the intercritical phases, as well as the characteristics of the clinical picture in both depressive and manic phases.

How does bipolar disorder arise?

Causal factors include:

genetic predisposition: in 50% of cases at least one parent of the patient is affected by a mood disorder; if you have a relative suffering from bipolar disorder, the risk of developing this morbid form is 10 times higher than that of a person without such familiarity;
environmental causes: frequent evidence of emotional abuse, parental neglect, sexual and physical abuse occurring in childhood.

These are rather frequent disorders, affecting an estimated percentage of individuals between 0.5 and 1.5% of the general population, although it can be stated that the prevalence of this diagnostic grouping is actually greater when the estimates include the bipolar disorders not otherwise specified (i.e., disorders with pronounced, disabling bipolar features that do not fully meet the diagnostic criteria of DSM-5, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition).

How is bipolar disorder treated?

Many psychiatrists are rather cautious about administering antidepressants to patients with bipolar disorders, even in the depressive phases, due to the possibility of inducing a switch (passage) from the depressive phase to the manic phase.

A certain percentage of clinicians even goes so far as not to prescribe antidepressants to depressed patients without clear manic episodes in their medical history, or to do so only very sparingly as regards the dosages and the period of administration, when there are only elements of suspicion of a predisposition to bipolar disorder (familiarity, hyperthymic or cyclothymic temperament, significant symptoms of agitation within the depressive picture, etc.).

The caution is motivated by the possibility that this category of drugs may bring out manic symptoms in patients who would not otherwise have presented this clinical picture.

Although the intention behind these concerns is legitimate and understandable, as it is based on the need to protect the patient from the risk of entering a phase of manic excitement, the approach to the matter does not always appear to be based on scientific data relating to the reliability /validity of diagnostic procedures (diagnosis of psychiatric pathology and risk estimation of manic switch) and effective induction rate of manic phases in bipolar patients exposed to antidepressant treatments.

Medications for bipolar disorder: A clinical management research

Recent Swedish research (Viktorin A., 2014), which appeared in the authoritative American Journal of Psychiatry, has produced very significant results full of potential relapses in the clinical management of bipolar depression.

The study was conducted using Swedish national registries and included 3,240 patients with bipolar disorder who had started antidepressant treatment and had not taken any antidepressants in the previous year.

The patients were grouped into two categories:

those who had received treatment with antidepressants alone;
those who had received a combined treatment of antidepressants plus mood stabilizers (drugs of choice in the treatment of this clinical case).

Do antidepressants increase the risk of manic phase?

The increased risk of developing a manic phase was seen only in patients taking antidepressant monotherapy.

Patients who received both antidepressants and mood stabilizers had no such increased risk of developing mania in the three months following a prescription.

In the still subsequent period (from the third to the ninth month from the start of treatment), this second grouping even showed a reduction in the risk of relapse into a manic phase.

The research therefore highlights the importance of avoiding monotherapy with antidepressants (i.e. without the concomitant administration of mood stabilizers) in bipolar patients.

Furthermore, if the data were to be confirmed by further research, these results could favor more rational decision-making processes with respect to drugs for the treatment of bipolar disorder in the depressive phase, but also in those patients who, while certainly not suffering from bipolar disorder, present a potential risk of experiencing antidepressant-induced symptoms of mania.

How to estimate the risk of manic phases

In the meantime, some procedural measures could help the clinician to produce even more realistic and plausible estimates of the risk of inducing mania:

accurate personal and family history;
clinical diagnostic interviews referring to the patient’s clinical history to be carried out with family members and close acquaintances (of course, once the patient’s consent has been obtained);
administration of ad hoc questionnaires such as the Mood Disorder Questionnaire (MDQ), easily available on the web, followed by an accurate discussion with the patient regarding the most significant answers;
structured diagnostic clinical interviews (type SCID-I and MINI-plus, with particular reference to modules on mood disorders);
standardized self-administered psychological tests such as the MMPI-2 and the new MMPI-2 RF.

Bipolar disorder, references

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fifth edition. DSM-5. American Psychiatric Publishing. Washington, DC. London, England

Garno JL, Goldberg JF, Ramirez PM, Ritzler BA. Impact fo childhood abuse on the clinical course of bipolar disorder. Br J Psychiatry. 2005 Feb;186:121-5. Erratum in: Br J Psychiatry. 2005 Apr;186:357.

Viktorin A, Lichtenstein P, Thase ME, Larsson H, Lundholm C, Magnusson PKE, Landén M. The Risk of Switch to Mania in Patients With Bipolar Disorder During Treatment With an Antidepressant Alone and in Combination. Am J Psychiatry 2014, Jun 17. doi: 10.1176/appi.ajp.2014.13111501

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