Akathisia with SSRIs

Bruxism mainly occurs in stage 2 sleep and REM sleep (Bader et ah, 1977). A relationship to stress and anxiety has been suggested, but the disorder can be chronic without apparent association with stress (Faulkner, 1990 Pierce et ah, 1995). It has been suggested that the central dopaminergic system may be involved in the modulation of sleep bruxism (Lobbezoo et al., 1997). Case reports indicate that bruxism can be induced by the SSRI paroxetine (Romanelli et al., 1996). The mechanism remains unclear possibilities include sleep disturbance, serotonergic-mediated inhibition of dopamine manifesting as akathisia, and SSRI-induced anxiety. SSRI-induced bruxism may respond to therapy with buspirone (Ellison et al., 1993). 

In various case reports in this chapter, we will find that akathisia can be found in combination with SSRI-induced mania and aggression. 

Extrapyramidal symptoms (including akathisia, dystonia, dyskinesia, tardive dyskinesia, parkinsonism, and brux-ism) have been reported in association with SSRIs, especially in the presence of predisposing factors (SEDA-14, 14 12). Current data suggest that SSRIs should be used with caution in patients with parkinsonism (see the monograph on fluoxetine). Concomitant treatment with neuroleptic drugs and high concentrations of SSRIs seems to predispose to extrapyramidal symptoms. Elderly patients and women are also at increased risk. 

Fluoxetine, along with sertraline, fluvoxamine, and paroxetine, belongs to the more recently developed group of SSRI. The clinical efficacy of SSRI is considered comparable to that of established antidepressants. Added advantages include absence of cardiotoxicity, fewer autonomic nervous side effects, and relative safety with overdosage. Fluoxetine causes loss of appetite and weight reduction. Its main adverse effects include overarousal, insomnia, tremor, akathisia, anxiety, and disturbances of sexual function. 

Behavioral activation. Adverse effects while on the SSRIs may include anxiety, restlessness, agitation, ak-athisia, jitteriness, disinhibition, and/or activation. The development of anxiety, restlessness, and agitation while on an antidepressant has been described as part of the complex and poorly self-described syndrome of akathisia (Kalda, 1993). Behavioral activation is variously reported as akathisia, jitteriness, disinhibition, activation, or agitation, and may represent overlapping or different phenomena. It is important for clinicians to discuss these potential symptoms with children and their parents, as the symptoms certainly can occur in the pediatric age group, and it is not known if there is an additional age-related risk. 

Tremor and akathisia also may occur. Management is the same as that for SSRI side effects. Bupropion is not associated with anticholinergic side effects, orthostatic hypotension, weight gain, or cardiac conduction changes. 

A number of clinical reports have described a syndrome of obsessive SSRI-induced suicidality and aggression that seems particular to these drugs, starting with Teicher et al. (1990). These cases bear some similarity to akathisia-driven suicidality, but compulsion toward self-harm is not accompanied by the specific symptoms of akathisia. They summarized, Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupation after 2-7 weeks of fluoxetine treatment (p. 207). Additional cases and potential mechanisms of action were analyzed by Teicher et al. (1993). 

The capacity for SSRIs to induce akathisia—and for akathisia to cause suicidality, aggression, and a worsening mental condition—is also recognized in the DSM-IV and the DSM-IV-TR in the section dealing with neuroleptic-induced akathisia. The DSM-IV-TR observes, Akathisia may be associated with dysphoria, irritability, aggression, or suicide attempts. It also mentions worsening of psychotic symptoms or behavioral dyscontrol. It then states, Serotonin-specific reuptake inhibitor antidepressant medications may produce akathisia that appears identical in phenomenology and treatment response to Neuroleptic-Induced Acute Akathisia (p. 801). 

Gerber and Lund (1998) reviewed the literature and located 127 case reports of SSRI-induced abnormal movements. These included akathisia (agitation with hyperactivity), tardive dyskinesia, parkinsonism, dystonia (muscle spasms), bruxism (tooth grinding), and related disorders. They found many additional case reports from the drug manufacturers, including 516 cases of parkinsonism and 76 cases of tardive dyskinesia. The term tardive dyskinesia is usually reserved for cases that are irreversible. 

The authors pointed out that it is important to recognize SSRI-induced akathisia, because increasing agitation and restlessness early in treatment can be mistaken for worsening depression. In addition, case reports have suggested that akathisia can be associated with suicidal impulses. 

Often a preferred treatment of anxious depression as well as major depressive disorder comorbid with anxiety disorders Withdrawal effects may be more likely than for some other SSRIs when discontinued (especially akathisia, restlessness, gastrointestinal symptoms, dizziness, tingling, dysesthesias, nausea, stomach cramps, restlessness)... 

Akathisia has also been reported with the SSRIs, especially fluoxetine, and with the tricyclic antidepressants. Failure to recognize antidepressant-induced akathisia may lead to urmecessary prescribing of antianxiety agents or neuroleptics. 

Clomipramine, fluvoxamine, sertraline, and fluoxetine are approved by the FDA for treatment of OCD in children and adolescents. Childhood and adult OCD appear to respond similarly to drug therapy. The SSRIs appear to be effective and well tolerated in treatment of OCD in children and are generally considered first-line agents. Treatment with an SSRI produces a favorable response in 75% of children and adolescents with OCD. A combination of SSRIs and CBT is preferred in most cases. In children, the most commonly described side effects of SSRI therapy include nausea, headache, tremor, gastrointestinal complaints, drowsiness, akathisia, insomnia, disinhibition, and agitation. Clomipramine was significantly better than placebo in the treatment of OCD in children and adolescents, with 75% of patients having a moderate to marked improvement. Clomipramine was also more effective than desipramine in children and adolescents. ... 

Most experts agree that the SSRIs are better tolerated than clomipramine. The SSRIs are less likely to cause cardiovascular, sedative, anticholinergic, and weight gain side effects. Clomipramine is less likely than the SSRIs to cause insomnia, akathisia, nausea, and diarrhea. Side effects may be more severe when larger doses are used and with faster dose escalation. Tolerance to adverse effects often develops over 6 to 8 weeks of treatment, and tolerance is more fikely to develop to nausea, diarrhea, sedation, diminished libido and/or orgasm, anxiety, restlessness, insomnia, and anticholinergic side effects than to akathisia. ... 

Nervous System A case series of 20 refractory SSRI-treated patients with obsessive-compulsive disorder (OCD) received a single dose of amisulpride (400 mg), with eight patients experiencing acute akathisia and two an exacerbation of their OCD [87 ]. Anoculogyric crisis is an acute dystonic reaction associated witii high-potency antipsychotics but has not been reported following discontinuation. A case of oculogyric crisis is reported after discontinuation of amisulpride in a 26-year-old male patient previously treated for 2 years [88 ]. 

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